• 


HISTOLOGY: 


NORMAL  AND  MORBID. 


BY 


EDWARD   K.  DUNHAM,  Pn.B.,  M.D., 

PROFESSOR  OF  GENERAL  PATHOLOGY,   BACTERIOLOGY,   AND  HYGIENE  IN  THE  UNIVERSITY 
AND  BELLE VUE  HOSPITAL  MEDICAL  COLLEGE,  NEW  YORK. 


ILLUSTRATED   WITH   363   ENGRAVINGS. 


LEA   BROTHERS  &  CO., 

NEW  YORK  AND  PHILADELPHIA 

1898. 


Entered  according  to  Act  of  Congress  in  the  year  1898,  by 

LEA   BROTHERS    &  CO., 
in  the  Office  of  the  Librarian  of  Congress,  at  Washington.     All  rights  reserved. 


ELECTROTYPED  BY  PRESS  OF 

WESTCOTT  &  THOMSON.  PHILADA.  WILLIAM  J.    DORNAN.    PHILADA. 


\\f\ssr\ 


PREFACE. 


IN  presenting  to  the  student  of  medicine  so  condensed  a  volume 
upon  normal  and  morbid  histology  an  explanation  of  the  author's 
purpose  may,  perhaps,  not  be  amiss. 

It  appears  to  the  writer  that  the  most  important  lesson  to  be 
derived  from  a  study  of  the  tissues  in  health  and  in  disease  is 
a  knowledge  of  the  constant  and  potent  activities  of  the  cells  to 
which  those  tissues  owe  both  their  origin  and  usefulness.  When 
the  body  develops  under  normal  conditions  those  cells  build  up  the 
tissues,  gradually  modifying  their  formative  activities  so  as  to  oc- 
casion a  diversity  of  structure  in  the  various  parts  of  the  body. 
During  this  developmental  epoch,  and  after  maturity  is  attained, 
the  activities  which  are  grouped  as  functional,  and  which  it  is  the 
lot  of  the  tissues  to  maintain,  are  also  carried  on  by  the  cells. 

But  in  order  that  these  manifold  cellular  activities  shall  be  of  the 
usual  or  "  normal  "  character,  the  conditions  under  which  they  are 
carried  on  must  not  depart  greatly  or  for  any  considerable  length 
of  time  from  a  certain  usual,  but  rather  indefinite  standard.  If 
those  conditions  are  materially  altered,  the  cellular  activities  become 
modified,  and  the  functions  they  perform  suffer  aberration,  as  a 
result  of  which  structural  changes  in  the  cells  and  tissues  may 
ensue. 

It  is  this  close  relation  between  cellular  activity  and  structure 
which  unifies  the  subjects  usually  kept  distinct  under  the  titles  of 
normal  and  pathological  histology,  for  it  is  evident  that  there  is  no 
natural  separation  between  those  subjects. 

In  the  preparation  of  this  manual  the  author  has  steadfastly  kept 
in  view  such  a  conception  of  the  relations  between  cellular  activity 
and  structure.  To  carry  out  this  purpose  it  did  not  appear  neces- 
sary to  describe  the  various  changes  wrought  in  the  individual 
organs  or  tissues  by  unusual  conditions.  It  seemed  to  him  that  a 
general  statement  of  the  alterations  in  structure  attributable  to 

3 


4  PREFACE. 

modified  cellular  activity  would  enable  the  student  to  interpret  such 
departures  from  the  normal  as  he  might  observe  in  particular  speci- 
mens, provided  he  was  familiar  with  the  normal  structures  of  the 
body.  In  this  belief  the  writer  has  devoted  most  of  his  space  to  a 
description  of  the  normal  structures,  and  has  contented  himself 
with  only  a  brief  account  of  the  histology  of  the  more  prevalent 
morbid  processes.  He  was  encouraged  in  this  course  by  the  con- 
sciousness that  in  individual  cases  the  application  of  the  principles 
involved  might  be  more  successfully  made  by  the  instructors  under 
whose  guidance  these  studies  were  pursued.  For  the  sake  of  clear- 
ness, however,  examples  of  morbid  structure  have  been  selected 
from  various  parts  of  the  body  to  illustrate  the  different  phases  of 
the  processes  that  were  being  outlined. 

Those  histological  methods  and  data  which  are  utilized  for  the 
purpose  of  clinical  diagnosis  have  been  almost  entirely  omitted,  be- 
cause they  are  fully  described  in  special  works  on  that  subject  and 
are  not  strictly  within  the  limits  assigned  to  this  more  elementary 
book. 

.  Occasional  reference  has  been  made  to  technical  journals  on  his- 
tology. Those  which  contain  abstracts  of  the  current  literature  on 
that  subject,  and  which  will,  therefore,  be  of  greatest  use  to  the 
student,  are :  The  Journal  of  the  Royal  Microscopical  Society,  Zeit- 
schrift  fur  wissenschaftliche  Mikroskopie,  and  Centralblatt  fur  allge- 
meine  Pathologic  und  pathologische  Anatomie.  The  student  is  also 
referred  to  Mallory  and  Wright's  Pathological  Technique,  Lee's  Mi- 
crotomist's  Vade  Mecum,  and  to  the  more  recent  German  revised 
edition,  Grundzuge  der  mikroskopischen  Technik,  by  Lee  and  Mayer. 
It  may  be  that  well-founded  exceptions  will  be  taken  to  some  of 
the  explanations  of  morbid  processes  which  are  here  offered  ;  but 
it  is  the  author's  hope  that  he  has  not  advanced  theoretical  views 
with  sufficient  emphasis  to  mislead  the  student.  Should  the  general 
plan  of  the  work  meet  with  a  kindly  reception,  it  will  be  his 
endeavor  to  correct,  in  a  future  edition,  such  errors  and  omissions 
as  may  be  revealed  by  friendly  criticism. 

E.   K.  D. 
NEW  YORK,  October,  1898. 


CONTENTS 


PAGE 

INTRODUCTION  17 


PAET   I. 
NORMAL   HISTOLOGY. 


CHAPTER  I. 

THE  CELL 27 

CHAPTER  II. 

THE   ELEMENTARY  TISSUES     41 

CHAPTER   III. 

THE   EPITHELIAL  TISSUES 45 

CHAPTER   IV. 

THE  CONNECTIVE  TISSUES 63 

CHAPTER  V. 

TISSUES  OF  SPECIAL   FUNCTION 82 

CHAPTER  VI. 
TISSUES  OF  SPECIAL  FUNCTION   (CONTINUED) 94 

CHAPTER  VII. 

THE  ORGANS 10(5 

5 


6  CONTENTS. 

CHAPTER   VIII. 

PAGE 

THE  CIKCULATOKY  SYSTEM 108 

CHAPTER  IX. 

THE  BLOOD  AND   LYMPH 122 

CHAPTER  X. 

THE   DIGESTIVE  ORGANS 128 

CHAPTER  XI. 

THE  LIVER 146 

CHAPTER  XII. 
THE  URINARY  ORGANS    .    .    - 153 

CHAPTER  XIII. 
THE   RESPIRATORY  ORGANS 168 

CHAPTER  XIV. 

THE  SPLEEN 176 

CHAPTER   XV. 

THE  DUCTLESS  GLANDS 180 

CHAPTER  XVI. 

THE  SKIN 195 

CHAPTER  XVII. 

THE  REPRODUCTIVE  ORGANS 207 

CHAPTER  XVIII. 
THE  CENTRAL  NERVOUS   SYSTEM 234 

CHAPTER  XIX. 

THE  ORGANS  OF  THE  SPECIAL  SENSES   .  .    252 


CONTENTS. 

PART   II. 
HISTOLOGY   OF   THE   MORBID   PROCESSES. 


CHAPTER  XX. 

PAGE 

DEGENERATIONS   AND   INFILTRATIONS  .    265 


CHAPTER  XXI. 

ATROPHY 284 

CHAPTER   XXII. 

HYPERTROPHY   AND  HYPERPLASIA 288 

CHAPTER   XXIII. 
METAPLASIA 291 

CHAPTER  XXIV. 

STRUCTURAL  CHANGES   DUE  TO   AND  FOLLOWING  DAMAGE    293 

CHAPTER   XXV. 
TUMORS    .  341 


PART   III. 
HISTOLOGICAL   TECHNIQUE. 


CHAPTER  XXVI. 

PRACTICAL   SUGGESTIONS  FOR  THE  CARE  AND  USE  OF  THE 

MICROSCOPE— MICROSCOPICAL  TECHNIQUE 397 


HISTOLOGY: 

NORMAL  AND  MORBID 


INTRODUCTION. 

DURING  life  all  parts  of  the  human  body  are  the  seat  of  constant 
activity.  This  is  a  fact  too  readily  overlooked  by  the  student  who 
gains  his  knowledge  of  the  structures  of  the  body  by  a  study  of  the 
tissues  after  death.  To  make  that  study  of  use  to  him  in  his  medi- 
cal thinking  he  should  constantly  bear  in  mind  that  he  is  viewing 
the  mechanism  of  the  body  while  it  is  at  rest,  and,  furthermore, 
that  the  methods  employed  in  the  study  of  the  minute  structure  of 
the  parts  not  only  arrest  the  normal  activities  of  those  parts,  but 
expose  them  to  mutilation.  He  must,  therefore,  constantly  supple- 
ment the  knowledge  of  structure  he  gains  by  his  histological  studies 
by  recalling  to  mind  and  applying  that  which  he  has  acquired  by 
a  study  of  physiology,  habitually  associating  his  ideas  of  structure 
and  functional  activity,  until  he  can  hardly  think  of  what  a  struct- 
ure is  without  at  once  recalling  what  it  does.  This  he  cannot  do 
till  he  has  mastered  at  least  the  general  outlines  of  systematic 
anatomy  and  of  physiology.  Those  two  fundamental  subjects  are 
brought  together  by  an  intelligent  study  of  the  minute  structure  of 
the  body,  histology,  which,  for  this  reason,  has  also  and  appro- 
priately been  called  physiological  anatomy. 

But  the  student  of  medicine  must  go  beyond  this.  To  the  con- 
ception of  the  body  during  health,  which  he  has  formed  by  this 
thoughtful  method,  he  must  then  add  a  conception  of  the  influence 
exerted,  both  on  the  structure  and  activities  of  the  body,  by  ab- 
normal conditions  which  disturb  or  thwart  the  usual  working  of 
that  complex  mechanism.  The  more  closely  he  can  make  those 
conceptions  agree  with  observed  facts,  the  more  perfect  will  become 
his  ability  to  interpret  the  physical  signs  and  symptoms  of  disease, 
2  17 


1 8  INTE  OD  UCTION. 

and  the  clearer  will  grow  his  insight  into  the  causes  and  tendencies 
of  the  processes  of  which  they  are  an  expression. 

In  all  his  studies  he  must  seek  not  merely  to  train  his  powers 
of  observation ;  he  must  endeavor  to  cultivate  his  ability  to  inter- 
pret what  he  sees ;  to  deduce  the  processes  and  causes  that  have 
wrought  the  results  he  perceives,  and  to  compare  those  deductions 
with  the  conceptions  of  living  things  he  has  already  formed,  so  that 
his  ideas  may  remain  in  perfect  accord  with  one  another  as  his  grasp 
of  the  subject  enlarges.  By  so  doing  he  may  hope  to  create  a  life- 
like mental  picture  of  the  body  both  in  health  and  during  disease. 

The  activities  of  the  body  involve  changes  in  the  substances  of 
which  it  is  composed.  Some  of  these  changes  are  always  destruc- 
tive in  character — that  is,  they  result  in  chemical  rearrangements 
which  convert  more  complex  combinations  of  less  stable  nature  into 
simpler  combinations  of  greater  stability.  Such  chemical  changes, 
whether  they  take  place  within  the  body  or  in  external  nature, 
among  organic  or  inorganic  substances,  are  always  accompanied  by 
a  liberation  of  energy  hitherto  locked  up  or  stored  in  latent  or 
potential  form  in  the  compounds  of  higher  complexity.  It  is  this 
liberated  or  kinetic  energy  which  is  utilized  by  the  bodily  mechan- 
ism for  the  performance  of  internal  or  external  work.  When 
directed  in  various  ways  and  operating  through  different  structures, 
this  energy  occasions  visible  movement,  appears  as  heat,  etc.,  or 
passes  again  into  the  latent  form  in  the  elaboration  of  more  com- 
plex chemical  substances  from  those  of  simpler  constitution. 

These  associated  transformations  of  matter  and  energy  involve  a 
continual  loss  to  the  bodily  economy.  The  stock  of  energy  is  dim- 
inished during  the  execution  of  external  work  and  by  the  dissipa- 
tion of  heat.  The  store  of  useful  chemical  substances  is  reduced 
by  their  progressive  conversion  into  compounds  that  are  insuscep- 
tible of  further  utilization,  and  which,  in  many  cases,  may  act  injuri- 
ously upon  the  structures  of  the  body.  Under  normal  conditions 
such  substances  are  eliminated  from  the  body. 

It  is  evident,  then,  that  the  body  is  constantly  suffering  a  loss  of 
both  energy  and  matter.  This  loss  must  be  made  good  if  the 
activities  of  the  body  are  to  be  maintained,  and  this  is  accomplished, 
during  health,  through  the  absorption  of  fresh  material,  containing 
latent  energy,  from  the  food  taken  into  the  body. 

The  activities  of  the  body  are  not  the  same  in  all  its  parts.  They 
are  all  alike  in  one  particular — namely,  that  each  part  must  main- 


INTRODUCTION.  19 

tain  its  own  nutrition,  incorporating  the  food-materials  that  are 
accessible  to  it  and  using  them  in  such  a  way  as  to  keep  its  struct- 
ure in  a  normal  condition.  But,  aside  from  this  duty  which  is  com- 
mon to  all,  each  part  has  a  duty  to  perform  for  the  good  of  the 
whole  organism ;  and,  as  we  shall  see,  this  duty  often  appears  to  be 
paramount,  the  activities  which  it  necessitates  being  carried  on 
even  if  they  involve  a  sacrifice  in  the  nutrition  or  structure  of  the 
individual  part. 

Each  part  of  the  body  has  some  particular  kinds  of  work  assigned 
to  it,  which  constitute  its  functions,  and  which  it  performs  for  the 
benefit  of  the  whole  body.  The  development  and  life-history  of 
each  part  has  direct  reference  to  those  functions,  through  which  it 
co-operates  with  all  the  other  parts  in  maintaining  the  integrity  and 
normal  activities  of  the  whole  body,  all  the  parts  being  interde- 
pendent upon  each  other  and  subservient  to  the  general  needs. 

The  foregoing  considerations  prepare  us  for  the  fact  that  the 
structure  of  the  various  parts  of  the  body  differs  in  its  details. 
The  study  of  those  finer  details  can  only  be  pursued  with  the  aid 
of  the  microscope,  for  the  microscopical  constituents  of  the  tissues 
are  the  elements  which  confer  upon  them  their  particular  properties 
and  powers.  This  study  is  called  histology. 

Investigation  has  shown  that  there  is  one  form  of  tissue-element 
which  is  always  present  in  all  parts  of  the  body.  This  is  the  cell. 
It  does  not  always  possess  the  same  form  or  internal  structure,  but 
in  all  its  variations  the  same  general  plan  of  construction  is  adhered 
to.  These  cells  are  the  essentially  active  constituents  of  the  tissues. 
It  is  within  them  that  the  transformations  of  matter  and  energy  are 
chiefly  carried  on,  and  it  is  due  to  their  activities  that  the  tissues 
forming  the  body  are  elaborated  and  enabled  to  perform  their  sev- 
eral functions.  These  marvellous  powers  possessed  by  the  cell 
have  created  our  conception  of  life,  and,  in  spite  of  eager  study, 
remain  inscrutable.  We  do  not  know  why  a  living  cell  differs  from 
a  dead  cell,  but  we  do  know  that  the  mysterious  vital  powers  are 
only  derived  from  pre-existent  living  cells  and  are  not  antagonistic 
to  the  chemical  and  physical  laws  governing  unorganized  matter. 

All  the  cells  of  the  body  are  descendants  of  a  single  cell,  the  egg, 
from  which  they  arise  by  successive  divisions,  and  throughout  the 
existence  of  the  body  they  retain  some  of  the  characters  of  the 
original  cell.  But  as  the  body  develops  the  cells  of  the  different 
parts  display  divergent  tendencies,  which  finally  result  in  the  for- 


20  INTRODUCTION. 

mation  of  a  considerable  variety  of  tissues,  grouped  in  various  ways 
to  form  organs  or  systems  of  very  different  kinds  of  utility  to  the 
whole  organism.  This  divergent  development  is  known  as  differen- 
tiation and  results  in  a  specialization  of  the  different  parts  of  the 
body.  Its  study  constitutes  embryology,  but  it  will  make  the  com- 
prehension of  histology  easier  if  some  of  the  simpler  and  broader  facts 
derived  from  a  study  of  development  are  first  briefly  summarized. 

A  new  individual  arises  through  the  detachment  of  a  single  cell, 
the  ovum  (Fig.  1),  from  the  parent  organism.     This  cell  divides 

FIG.  1. 


Section  of  human  ovum  and  its  immediate  surroundings  within  the  ovary.  (Nagel.)  a,  zona 
pellucida ;  b,  cytoplasm  of  the  ovum  ;  c,  granules  and  globules  of  stored  food  materials 
within  the  cytoplasm,  collectively  known  as  the  metaplasm  or  deutoplasm;  d,  germinal 
vesicle  or  nucleus  of  the  ovum  containing,  in  this  case,  two  germinal  spots  or  nucleoli ; 
e,  zone  of  epithelial  cells  immediately  surrounding  the  ovum  ;  /,  cells  of  the  discus  pro- 
ligerus  ;  g,  perivitelline  spaces  separating  the  zona  pellucida  from  the  cytoplasm  of  the 
ovum. 

into  two  cells,  which,  even  at  this  stage  of  development,  differ 
slightly  from  each  other.  These  daughter-cells  in  turn  divide  in 
two,  and  this  process  of  division  is  continued,  each  cell  giving  rise 
to  two  new  cells,  until  a  considerable  aggregate  of  cells  has  resulted 
(Fig.  2).  Then  the  cells  assume  a  definite  arrangement  into  layers. 
Some  become  disposed  in  a  superficial  layer  enclosing  the  rest  of 
the  cells  and  a  body  of  fluid.  This  layer  is  called  the  primitive 
ectoderm.  The  remaining  cells  accumulate  in  an  irregular  laminar 
mass  beneath  the  primitive  ectoderm  at  the  site  of  the  future  em- 
bryo. This  mass  of  cells  is  the  primitive  entoderm.  Thus,  at 


INTRODUCTION. 


21 


this  stage  of  development,  there  is  a  cellular  sac,  containing  fluid, 
with  a  reinforcement  of  its  wall  at  the  region  occupied  by  the  primi- 
tive entoderm  (Fig.  3). 


FIG. 


Segmented  egg  of  Petromyzon  Planeri :  Surface  view  of  the  collection  of  cells.    The  nuclei 

are  invisible.    (Kupffer.) 

Subsequent  to  these  events  a  third  layer  of  cells  becomes  inter- 
posed between  the  primitive  ectoderm  and  entoderm.     Most  of  its 

FIG.  3. 


Ovum  of  rabbit :   a,  primitive  ectoderm  in  section ;  6,  primitive  ectoderm,  surface  view ; 
c,  primitive  entoderm  ;  d,  dividing  cell  of  the  ectoderm,    (van  Beneden.) 

cells  are  derived  from  those  of  the   primitive   ectoderm,   but  the 


22  INTRODUCTION. 

primitive  entoderm  may  also  participate  in  its  formation.  This 
third  layer  is  called  the  mesoderm.  Soon  after  its  formation,  the 
mesoderm  divides  at  the  sides  of  the  embryo  into  two  layers — a 
parietal,  which  joins  the  under  surface  of  the  ectoderm,  and  a  vis- 
ceral, attached  to  the  upper  surface  of  the  entoderm.  The  space 
between  these  two  layers  is  occupied  by  fluid,  and  is  destined  to 
form  the  future  body-cavities.  In  the  axis  of  the  embryo  the  three 
earlier  layers  remain  in  continuity,  forming  a  cellular  mass  around 
the  site  of  the  future  spinal  column  (Fig.  4). 


FIG.  4. 


ect 


"mend 


Embryo  of  Necterus  in  cross-section.    (Platt.)    ect.,  ectoderm  ;  mend.,  mesoderm  ;  end.,  ento- 
derm ;  a,  neural  groove ;  ch,  site  of  future  spinal  column. 

From  these  three  embryonic  layers  of  cells  the  body  of  the  foetus 
is  developed.  The  entoderm,  with  the  visceral  or  lower  layer  of  the 
mesoderm,  turns  downward  and  inward  to  meet  its  fellow  of  the 
opposite  side  and  form  the  alimentary  tract.  The  ectoderm  and 
parietal  or  upper  layer  of  the  mesoderm  also  turn  downward  and  in- 
ward, outside  of  the  alimentary  tube,  and  join  those  of  the  other  side 
to  form  the  walls  of  the  body. 

Meanwhile,  the  upper  surface  of  the  ectoderm  over  the  axis  of  the 
embryo  becomes  furrowed.  The  edges  of  this  furrow  grow  upward, 
deepening  the  groove  between  them,  and  finally  arch  over  it  and 
coalesce,  forming  a  canal  around  which  the  central  nervous  system 
is  developed  (Fig.  5).  Traces  of  this  canal  persist  through  life  as 
the  central  canal  of  the  spinal  cord  and  the  ventricles  of  the  brain. 

The  embryonic  layers  have  a  deeper  significance  than  the  mere 
furnishing  of  the  architectural  materials  from  which  the  body  is 
built  up.  They  are  evidences  of  a  distinct  differentiation  in  the 
development  of  the  cells  of  which  they  are  composed.  The  ecto- 
derm gives  rise  to  the  functional  part  of  the  nervous  system  and  to 
the  epithelial  structures  of  the  skin  and  its  appendages.  The  cells 
of  the  mesoderm  elaborate  the  muscular  tissues  and  that  great  group 


INTR  OD  UCTION.  23 

known  as  the  connective  tissues,  and  the  entoderm  contains  the 
cells  that  build  up  the  linings  of  the  digestive  tract,  including  its 
glands,  and  of  the  respiratory  organs.  It  appears,  then,  that  this 
division  of  the  cells  of  the  embryo  into  three  layers  marks  a  dis- 
tinct difference  in  the  destinies  of  the  cells  composing  those  layers. 
This  distinction  persists  through  life,  the  tissues  arising  from  a  given 
layer  showing,  in  general,  a  closer  relationship  to  each  other  than 
the  tissues  arising  from  different  layers.  But  this  relationship  is 
not  always  revealed  by  a  similarity  in  ^structure,  for  the  latter  is 
determined  by  the  functions  the  tissues  are  destined  to  perform, 
and  tissues  of  like  function  acquire  a  similarity  in  structure.  Thus, 
for  example,  the  neuroglia  in  the  central  nervous  system  resembles 

FTG.  5. 


Cross-section  of  fish  embryo.  (Ziegler.)  a,  neural  canal,  cells  enclosing  it  not  represented; 
6,  chorda  dorsalis,  site  of  future  spinal  column ;  ao,  aorta  ;  Bf,  external  layer  of  meso- 
derm ;  c,  c,  body-cavity ;  d,  alimentary  canal,  not  yet  completely  closed  *  *,  passes 
through  the  external  layer  of  the  mesoderm  to  its  inner  surface  ;  e,  deutoplasm,  or  yolk 
of  egg. 

some  of  the  connective  tissues,  although  one  develops  from  the 
ectoderm  and  the  other  from  the  mesoderm ;  and  the  ganglion  cells 
of  the  central  nervous  system  differ  greatly  in  structure  from  the 
epithelium  of  the  skin,  nails,  etc.,  and  the  cells  of  the  neuroglia, 
notwithstanding  the  fact  that  they  all  spring  from  the  cells  of  the 
ectoderm.  The  explanation  is  to  be  sought  in  the  similarity  of  the 
usefulness  of  neuroglia  and  connective  tissue  and  the  difference  in 
the  functions  of  ganglion  cells  and  those  of  the  other  tissues  eman- 
ating from  the  ectoderm. 

During  the  early  stages  of  development  the  cells  of  the  germinal 
layers  are  very  similar  in  character,  although,  as  we  have  seen, 
their  potential  qualities  are  quite  diverse.  As  growth  proceeds, 
they  begin  to  vary  in  size,  shape,  and  internal  structure  in  the  dif- 


24  INTR  OD  UCTION, 

ferent  parts  of  the  foetus.  Their  relative  positions  become  modi- 
fied. The  primitive  organs  are  defined  and  the  tissues  of  which 
they  are  composed  become  elaborated. 

The  elaboration  of  the  tissues  is  wrought  by  the  cells,  which  dis- 
play what  is  called  their  formative  powers  in  the  production  of 
materials  of  various  sorts  which  lie  between  them,  and  are  called 
the  intercellular  substances.  The  amount  and  kind  of  intercellular 
substance  vary,  each  form  of  tissue  having  its  own  peculiarities  in 
this  respect,  dependent  upon  the  role  it  is  to  play  in  the  general 
economy.  Some  of  the  tissues  perform  functions  which  require  the 
active  processes  that  can  be  carried  on  only  in  cells,  and  in  these 
the  intercellular  substances  are  either  small  in  amount  and  appar- 
ently structureless,  as  in  epithelium,  or  their  place  is  taken  by  a 
tissue  of  separate  origin,  while  the  cells,  relieved  of  the  necessity 
for  exercising  their  formative  powers  in  this  direction,  become 
highly  specialized  to  meet  the  functional  demands  imposed  upon 
them.  This  development  is  met  with  in  the  muscular  and  nervous 
tissues. 

Other  tissues  of  the  body  are  of  use  mainly  because  of  their 
physical  properties,  such  as  rigidity,  elasticity,  tensile  strength,  plia- 
bility, etc.  These  tissues,  collectively  called  the  connective  tissues, 
are  essentially  passive.  They  require  little  or  no  cellular  activity 
for  the  performance  of  their  functions,  and  it  is  in  the  elaboration 
of  these  tissues  that  the  cells  exercise  their  most  marked  formative 
powers  during  the  development  of  the  body,  causing  the  deposition 
of  intercellular  substances  which  possess  the  requisite  physical  char- 
acters— rigidity  and  elasticity  in  the  case  of  bone,  pliability  and  ten- 
sile strength  in  the  case  of  ligamentous  structures,  etc.  As  these 
substances  are  perfected,  the  cells  decrease  in  activity,  until  they 
merely  preside  over  the  integrity  of  the  intercellular  substances  they 
have  already  produced. 

It  may  be  well  to  point  out  here  a  distinction  that  divides  the 
tissues  of  active  cellular  function  into  two  groups.  The  first  group, 
including  the  various  modifications  of  epithelium,  displays  its  ac- 
tivity in  the  elaboration  of  material  products,  taking  the  form  of 
either  new  cells  which  are  continually  being  produced,  or  of  certain 
chemical  substances  which  appear  as  a  secretion.  The  second 
group,  comprising  the  muscular  and  nervous  tissues,  exercises  its 
functional  activities  in  the  storage  of  latent  energy  in  such  sub- 
stances of  unstable  chemical  nature  and  in  such  a  manner  that  it 


INTRODUCTION.  25 

can  be  liberated  when  required  and  directed  toward  the  accomplish- 
ment of  some  definite  purpose.  The  functions  of  both  groups 
require  an  active  intracellular  metabolism,  resulting  in  the  forma- 
tion of  particular  chemical  substances.  In  this  they  are  alike. 
But  in  the  first  group  the  production  of  those  substances  is,  in 
itself,  the  functional  purpose  of  the  process,  while  in  the  second 
group  those  substances  are  merely  a  means  for  holding  energy  in 
the  latent  condition.  If  we  may  so  express  ourselves,  the  first 
group  utilizes  energy  for  the  elaboration  of  material,  the  second 
group  elaborates  material  for  the  utilization  of  energy. 

In  the  adult,  under  normal  conditions,  each  kind  .of  cell,  if  it 
reproduce  at  all,  gives  rise  to  cells  only  of  its  own  kind.  But  when 
the  conditions  are  morbid,  a  sort  of  reversion  may  take  place,  the 
progeny  of  a  given  cell  then  showing  less  evidence  of  specialization 
than  the  parent  cell.  Such  reverted  cells,  or  their  descendants,  may 
never  develop  into  more  specialized  cells,  or  they  may  regain  the 
original  degree  of  specialization  possessed  by  the  first  cell,  or,  fin- 
ally, they  may  become  specialized  along  some  divergent  line  of  devel- 
opment, giving  rise  to  a  tissue  that  is  nearly  or  remotely  akin  to 
that  from  which  they  started,  according  to  the  degree  of  reversion 
which  has  taken  place.  The  reversion  appears  never  to  extend 
further  back  than  the  degree  of  specialization  that  is  marked  by 
the  formation  of  the  three  embryonic  layers  in  the  history  of  devel- 
opment ;  for  example,  epithelium  which  springs  from  either  the 
entoderm  or  ectoderm  does  not  revert  to  a  primitive  condition  from 
which  it  can  develop  into  bone  or  some  other  form  of  connective 
tissue  normally  derived  from  the  mesoderm.  Examples  of  rever- 
sion will  be  met  with  in  the  chapters  on  Inflammation,  Tumors,  and 
Metaplasia. 


PART  I. 
NOEMAL    HISTOLOGY. 


CHAPTER  I. 
THE  CELL. 

As  has  been  stated  in  the  introductory  chapter,  the  cells  of  the 
body  are  not  all  alike.  Most  of  them  have  undergone  modifications 
fitting  them  for  the  performance  of  some  definite  function,  and  the 
majority  of  them  are  in  consequence  not  appropriate  objects  for  a 
study  of  the  general  characters  of  a  cell.  The  extent  to  which  this 
modification  has  affected  the  visible  structure  of  the  cell  is,  how- 
ever, very  different  in  the  different  tissues,  and  in  some  of  them  the 
cells  retain  so  much  of  their  original  embryonic  appearance  as  to 
closely  resemble  the  unspecialized  cell. 

This  is  true  of  the  cells  of  some  varieties  of  epithelium.  But, 
though  in  appearance  they  give  little  evidence  of  specialization,  in 
their  functional  activities  they  display  very  marked  modifications  of 
the  powers  of  the  primitive  cell.  Some  of  those  powers,  perhaps 
the  nutritive,  perhaps  the  secretory,  have  become  exaggerated,  while 
others,  e.  g.,  the  loeomotory,  or  reproductive,  have  fallen  into  abey- 
ance, or  suffered  almost  total  extinction. 

On  the  other  hand,  it  is  obvious  that  such  cells  as  constitute  the 
whole  body  of  unicellular  animals  must  retain  all  the  powers  essen- 
tial to  a  living  cell  in  relatively  equal  states  of  development.  No 
one  of  them  can  be  extinguished  or  thrown  out  of  its  proper  bal- 
ance with  respect  to  the  others  if  the  cell  is  to  remain  normal. 
And  yet,  even  among  the  unicellular  organisms,  certain  parts  of  the 
cell  may  be  very  evidently  specialized  for  the  performance  of  par- 
ticular functions.  For  example,  the  cilia  of  infusoria  have  the 
power  of  executing  much  more  rapid  movements  than  the  other 

27 


28 


NORMAL  HISTOLOGY. 


parts  of  the  same  cell.  And  it  is  probable  that  all  protozoa,  i.  e. 
unicellular  animals,  possess  similar,  though  less  obvious  and  in- 
ternal, heterogeneity  of  constitution. 

The  less  the  degree  of  specialization  or  differentiation  in  the 
structure  of  an  organism,  the  less  highly  developed  is  the  functional 
activity  of  which  it  is  capable,  and  the  less  perfect  its  ability  to 
cope  with  possible  unfavorable  environment.  The  value  to  the 
whole  organism  of  a  diversity  in  its  parts  is,  therefore,  unquestion- 
able, and  the  higher  we  go  in  the  animal  kingdom,  the  greater  we 
find  the  development  of  this  diversity,  coupled  with  a  more  and 
more  perfectly  adjusted  co-operative  interdependence  of  the  differ- 
ent  parts  of  the  body. 

In  the  protozoa  the  single  cell  does  all  the  work  of  the  whole 
organism.  In  the  multicellular  animals,  the  metazoa,  this  work  is 
distributed  among  the  component  cells  of  the  body,  each  of  which 
has  developed  an  efficiency  for  performing  its  special  work  that 
would  be  incompatible  with  a  wider  range  of  duties. 

It  is  quite  impossible  to  find  in  nature  any  example  of  a  cell 
devoid  of  all  individual  peculiarities  attributable  to  differentiation 
or  specialization.  We  must,  therefore,  study  several  varieties  of 

FIG.  6. 


Amoeba  pellucida.    (Frenzel.)    a,  ectoplasm ;  b,  endoplasm ;  c,  nucleus ;  d,  nucleolus  ;  e,  large 
contractile  vacuole  ;  /,  incorporated  foreign  body ;  g,  g,  pseudopodia. 

cell  in  order  to  gain  an  ideal  conception  of  such  a  cell.  This  accom- 
plished, we  may  consider  those  cells  which  occur  in  nature  as  special 
modifications  of  that  type. 

Perhaps  the  simplest  cell  leading  an  independent  existence  is  the 
protozoon,  amoeba  (Fig.  6).     This  animal  is  widely  distributed  in 


THE  CELL.  29 

moist  earth,  upon  the  surfaces  of  aquatic  plants,  and  in  the  soil  at 
the  margins  of  ponds  and  sluggish  streams. 

The  body  of  the  amoeba  consists  of  a  gelatinoid  substance  which 
has  received  the  name  protoplasm,  or,  more  definitely,  cytoplasm. 
Within  this  cytoplasm  and  sharply  defined  from  it  is  a  round  or 
oval,  vesicular  body,  called  the  nucleus,  which  in  turn  contains  one 
or  more  particularly  conspicuous  granules,  the  nucleoli. 

The  most  superficial  layer  of  the  cytoplasm  appears  perfectly 
clear,  colorless,  and  homogeneous.  It  envelops  the  rest  of  the  cyto- 
plasm, which  has  a  granular  appearance.  The  clear  peripheral 
portion  is  distinguished  as  the  "  hyaloplasm,"  or  "  ectoplasm  ;"  the 
granular  internal  portion  as  "  spongioplasm,"  or  "  endoplasm." 
The  terms  hyaloplasm  and  spongioplasm  are  also  .used  in  a  different 
and  more  restricted  sense,  as  will  presently  appear. 

When  viewed  under  the  microscope,  the  granules  of  the  cyto- 
plasm are  seen  to  possess  a  constant,  slight,  vibratile  motion,  the 
Brownian  movement,  to  which  is  added  now  and  then  a  flowing 
movement  from  one  part  of  the  cell  to  another.  At  intervals  there 
is  a  protrusion  of  the  ectoplasm  at  some  point,  extending  for  some 
distance  from  the  body  of  the  cell,  a  pseudopodium.  This  may  soon 
be  retracted  again,  merging  with  the  rest  of  the  ectoplasm,  or  some 
of  the  endoplasm  may  flow  into  the  central  portion  of  the  pseudo- 
podium,  converting  it  into  a  broad  extension  of  the  cell-body.  This 
may  subsequently  be  withdrawn,  or  the  whole  mass  of  cytoplasm, 
with  the  nucleus,  may  flow  into  the  pseudopodium,  gradually  in- 
creasing its  size,  until  the  whole  cell  occupies  the  original  site  of  the 
pseudopodium.  In  this  way  the  animal  executes  a  slow,  creeping 
locomotion. 

These  pseudopodial  movements  and  the  locomotion  occasionally 
incident  to  them  appear  to  be  wholly  spontaneous,  i.  e.  dependent 
upon  internal  conditions  of  which  we  have  no  knowledge.  They 
may,  however,  be  influenced  by  external  circumstances.  Certain  sub- 
stances evidently  attract  the  amoeba,  others  are  either  matters  of  in- 
difference to  it  or  repel  it.  If  a  pseudopodium  comes  in  contact  with 
some  particle  in  the  surrounding  medium,  it  may  retreat  from  it, 
appear  indifferent  to  it,  or  be  attracted  and  proceed  to  incorporate 
it.  This  is  accomplished  by  the  cytoplasm  flowing  around  the  for- 
eign body  and  coalescing  on  its  further  side  so  as  to  enclose  it.  It 
is  then  conveyed  to  the  body  of  the  cell,  either  by  cytoplasmic  cur- 
rents, by  the  withdrawal  of  the  pseudopodium  containing  it,  or 


30  NORMAL  HISTOLOGY. 

by  the  streaming  of  the  cell-body  into  that  protrusion.  The 
fate  of  the  particle  thus  incorporated  depends  upon  its  nature. 
If  it  be  serviceable  as  food,  it  is  gradually  digested  and  ab- 
sorbed, or  such  parts  of  it  as  are  digestible  are  so  utilized,  and 
the  remainder,  no  longer  of  use  to  the  amoeba,  is  extruded  from 
its  body. 

These  phenomena  reveal  powers  of  perception  and  selection  on 
the  part  of  this  cell  which  are  very  closely  akin  to  the  intelligence 
of  more  complex  organisms.  They  also  demonstrate  its  power  of 
assimilating  material  from  without,  to  serve  as  nourishment  and  the 
source  of  the  energy  which  it  expends  in  executing  its  movements 
and  in  carrying  on  the  chemical  processes  pertaining  to  its  internal 
economy. 

At  intervals,  there  appears  within  the  endoplasm  a  small,  clear, 
spherical  spot.  This  gradually  increases  in  size  and  constitutes  a 
little  drop  of  fluid,  sharply  defined  from  the  surrounding  cytoplasm. 
After  it  has  attained  a  certain  size,  it  suddenly  disappears,  the  cyto- 
plasm around  it  coalescing  and  leaving  no  trace  of  its  existence. 
Such  a  clear  space,  filled  with  fluid,  within  the  body  of  a  cell  is 
called  a  vacuole,  and  those  which  are  suddenly  obliterated,  contrac- 
tile vacuoles.  Their  purpose  is  not  clearly  understood,  but  prob- 
ably has  to  do  with  a  primitive  circulatory  or  respiratory  function, 
since  contractile  vacuoles  are  not  observed  in  the  cells  of  higher 
organisms  where  those  functions  are  carried  on  by  more  elaborate 
mechanisms. 

Eventually  the  amoeba  reproduces  its  kind  by  dividing  into  two 
similar  cells,  each  of  which  grows  into  a  likeness  to  the  parent 
individual. 

Let  us  now  compare  the  amoeba  with  some  other  varieties  of  cell, 
in  order  to  learn  what  they  all  have  in  common. 

The  amoeba  has  an  outer,  soft,  transparent  layer  of  cytoplasm, 
the  ectoplasm.  This  is  not  present  in  all  cells.  In  many  the 
granular  cytoplasm  has  no  envelope,  but  appears  to  be  quite  naked. 
In  other  varieties  it  is  enclosed  in  a  distinct  membrane. 

In  the  great  majority  of  cells  the  active  streaming  of  the  cyto- 
plasm and  the  pseudopodial  protrusions  described  in  the  amoeba  are 
wanting,  but  the  Brownian  movement  of  the  granules  is  more  con- 
stantly present.  The  cells  have  fixed  positions  and  their  food  is 
brought  to  them,  usually  in  solution,  so  that  the  more  active  move- 
ments so  essential  to  the  welfare  of  the  amoeba  would  be  superfluous. 


THE  CELL. 


31 


For  a  similar  reason,  as  already  intimated,  they  can  dispense  with 
the  contractile  vacuole. 

We  learn,  then,  that  when  we  reduce  the  cell  to  its  simplest 
terms,  it  consists  of  a  mass  of  cytoplasm  enclosing  a  nucleus.  To 
these  we  must  probably  add  a  third  essential  constituent,  the  Centro- 
some,  which  is  a  minute  granule  situated  in  the  cytoplasm.  It  is  so 
small  that  its  presence  has  not  been  established  in  all  cells,  its  detec- 
tion in  many  cells  being  extremely  difficult  because  of  the  general 
granular  appearance  of  the  cytoplasm  in  which  it  lies.  It  plays  such 
an  important  part,  however,  in  the  division  of  those  cells  in  which 
it  has  been  studied,  that  the  inference  that  it  is  an  essential  part  of 
all  cells  appears  justified. 

These  three  constituents,  the  cytoplasm,  nucleus,  and  centrosome, 
appear  to  be  the  essential  organs  of  a  cell  among  which  its  activities 
are  distributed  (Fig.  7).  We  do  not  know  how  they  do  their  work, 

FIG.  7. 


Schematic  diagram  of  a  cell :  a.  ectoplasm  composed  of  hyaloplasm ;  b,  spongioplasm ;  c, 
chromosome,  composed  of  "chromatin,"  and  forming  a  part  of  the  intranuclear  reticu- 
lum ;  between  these  chromatic  fibres  is  the  achromatin ;  d,  hyaloplasm  in  the  meshes  of 
the  spongioplasm ;  e,  one  of  the  two  nucleoli  represented  in  the  diagram ;  /,  one  of  eight 
bodies  constituting  the  metaplasm  represented ;  g,  centrosome,  with  radiate  arrangement 
of  the  surrounding  spongioplasm ;  h,  nuclear  membrane. 

but  we  have  a  general  conception  of  the  distribution  of  the  work 
performed  by  the  whole  cell  among  these  three  organs. 


32  NORMAL  HISTOLOGY. 

1.  The  cytoplasm,  which  usually  makes  up  the  chief  bulk  of  the 
cell,  especially  in  those  varieties  which  have  active  metabolic  functions, 
appears  to  be  the  part  of  the  cell  in  which  the  assimilated  food  is  utilized 
in  the  production  of  chemical  substances,  either  fresh  cytoplasm  or 
some  other  product,  or  in  the  execution  of  movements  or  the  libe- 
ration of  energy  in  other  forms.     Most  of  the  active  processes  that 
•arc  obvious  seem  to  be  carried  on  in  the  cytoplasm  during  the  greater 
part  of  the  life-history  of  the  cell. 

2.  The  nucleus  appears  to  preside  over  the  assimilative  processes 
within  the  cell.     If  a  cell  be  subdivided  so  that  the  uninjured  nu- 
cleus is  retained  in  one  of  the  portions,  that  portion  may  grow  and 
become  a  perfect  cell.     But  the  portions  that  are  deprived  of  a  nu- 
cleus do  not  grow,  and  while  they  may  retain  life  for  a  considerable 
time,  utilizing  the  assimilated  food  they  retain,  eventually  perish. 

Aside  from  this  assimilative  function,  the  nucleus  appears  to  be 
the  carrier  of  hereditary  characters  from  the  parent  cell  to  its  prog- 
eny during  the  division  of  the  cell.  This  will  become  clearer  when 
the  process  of  cell-division  is  described. 

3.  The  centrosome  appears  to  be  the  organ  presiding  over  the 
division  of  the  cell.     It  inaugurates  those  activities  in  nucleus  and 
cytoplasm  which  result  in  the  production  of  new  cells,  and  seems  to 
guide  them,  at  least  during  the  greater  part  of  the  whole  process. 

It  is  evident,  from  these  statements,  that  the  cell  has  an  exceed- 
ingly complex  organization,  which  a  simple  microscopical  study  can- 
not wholly  reveal.  Notwithstanding  this  fact,  obvious  microscopical 
differences  are  presented  by  cells  which  have  become  specialized  in 
different  directions,  and  we  must  know  something  of  the  visible 
structure  of  the  primitive  cell  before  we  can  appreciate  these  depart- 
ures from  it. 

The  cytoplasm  is  not  a  simple  substance.  Its  constitution  is  so  com- 
plex that  our  present  means  of  research  are  not  adequate  to  reveal 
its  structure.  We  know  that  its  solid  constituents  are  chiefly  pro- 
teids,  together  with  relatively  small  quantities  of  carbohydrates,  fats, 
and  salts.  To  these  is  added  a  large  proportion  of  water  which, 
while  not  entering  into  a  definite  chemical  union  with  the  other 
constituents,  is  so  intimately  associated  with  them  as  to  form  an 
integral  part  of  the  cytoplasm. 

The  visible  structure  of  cytoplasm  differs  somewhat  in  different 
cells,  even  among  those  that  appear  to  be  comparatively  unspecial- 
ized.  In  the  fixed  cells  of  the  higher  animals  and  man  it  appears 


THE  CELL.  33 

to  consist  of  a  very  delicate  network  or  reticulum  of  minute  fibres, 
termed  the  spongioplasm.  The  points  of  junction  of  these  fibres 
and  their  optical  cross-sections  give  a  finely  granular  appearance  to 
the  cytoplasm. 

In  the  meshes  of  the  spongioplasm  is  a  clear,  homogeneous  sub- 
stance, the  hyaloplasm.  This  may  also  contain  some  granules,  but 
they  are  probably  not  constituent  parts  of  the  cytoplasm  and  are 
grouped  under  the  term  metaplasm.  Some  of  them  are  composed 
of  material  taken  from  without,  either  in  their  original  form  or 
slightly  modified ;  others  have  been  produced  within  the  cell  by 
chemical  transformations,  and  are  either  useful  products,  to  be  sub- 
sequently turned  to  account  by  the  cell  itself  or  to  be  discharged  as 
a  secretion,  or  they  are  waste  matter  destined  for  elimination  from 
the  body. 

The  relative  proportions  of  the  hyaloplasm  and  the  spongioplasm 
and  the  arrangement  of  the  fibres  of  the  latter  both  vary  in  differ- 
ent cells.1 

When  seen  under  the  microscope  the  structure  of  the  nucleus, 
except  during  the  division  of  the  cell,  closely  resembles  that  of  the 
cytoplasm.  It  is  traversed  by  a  number  of  delicate  fibres,  which 
branch  and  give  the  nucleus  a  reticulated  appearance.  At  its  sur- 
face these  filaments  unite  to  form  a  delicate  membranous  envelope, 
sharply  defining  the  nucleus  from  the  surrounding  cytoplasm,  but 
it  is  a  question  whether  this  membrane  is  continuous,  or  whether  it 
is  an  exceedingly  close  meshwork  with  minute  apertures  permitting 
a  direct  communication  between  the  cytoplasm  and  the  interior  of 
the  nucleus. 

The  spaces  between  the  nuclear  filaments  are  occupied  by  a  clear, 
homogeneous  substance,  which  may  be  identical  and  continuous  with 
the  hyaloplasm  of  the  rest  of  the  cell. 

One  or  more  highly  refracting  bodies,  the  nucleoli,  may  be  pres- 
ent in  the  nucleus,  lying  freely  in  the  clear  substance  between  the 
filaments  or  attached  to  the  latter.  Their  purpose  is  not  known, 
but  it  is  thought  that  they  are  not  essential  parts  of  the  cell  but 
correspond  more  or  less  closely  to  the  metaplasm  in  the  cell-body. 

1  The  reticulated  appearance  of  the  cytoplasm  may  also  be  explained  by  assum- 
ing it  to  have  an  alveolar  structure,  and  the  theory  that  such  is  its  actual  structure 
possesses  much  plausibility.  In  that  case  the  visible  reticulum  would  be  formed  by 
the  walls  of  the  alveoli  and  their  lines  and  points  of  intersection,  all  of  which 
would  be  included  in  the  spongioplasm,  while  the  contents  of  the  alveoli  would 
constitute  the  hyaloplasm. 
3 


34  NORMAL  HISTOLOGY. 

Owing  to  their  affinity  for  certain  coloring  matters,  the  substances 
composing  the  nuclear  filaments  are  called  chromatin,  or  chromo- 
plasrn.  The  hyaline  substances  making  up  the  rest  of  the  nucleus 
do  not  receive  those  coloring  matters,  and  for  this  reason  and  in 
this  situation  are  called  achromatin.  These  terms  are  only  used  in 
a  morphological  sense  and  do  not  specify  any  definite  chemical  com- 
pounds. The  behavior  of  the  nucleoli  toward  dyes  is  somewhat 
different  from  that  of  the  chromoplasm,  which  leads  to  the  inference 
that  they  are  of  a  different  chemical  nature. 

Except  during  cell-division,  the  nucleus  usually  lies  quiescent 
within  the  cytoplasm,  but  some  observers  have  seen  it  execute  ap- 
parently spontaneous  movements,  and  it  is  evidently  possible  for  its 
position  in  the  cell  to  vary  from  time  to  time. 

In  marked  contrast  to  this  apparently  dormant  state,  as  far  as 
visible  alterations  of  structure  are  concerned,  is  the  role  played  by 
the  nucleus  during  the  reproduction  of  the  cell. 

There  are  two  modes  of  cell-division,  the  "  indirect  "  and  the 
"  direct,"  but  they  are  by  no  means  equivalent  to  each  other.  The 
former,  also  termed  karyokinesis  because  of  the  active  changes  in 
the  nucleus,  appears  to  be  the  only  truly  reproductive  process. 
Direct  cell-division  results  in  the  formation  of  new  cells,  but  they 
seem  to  lack  that  perfection  of  organization  which  would  be  required 
for  the  complete  and  indefinite  transmission  of  all  the  characters  of 
the  parent  cells. 

Before  entering  into  a  description  of  karyokinesis,  a  few  words 
must  be  said  concerning  the  centrosome.  This  is  an  extremely  min- 
ute granule  which  is  usually  situated  in  the  cytoplasm  not  far  from 
the  nucleus.  It  is  often  surrounded  by  a  thin  zone  of  hyaloplasm 
which  facilitates  its  recognition  among  the  fibres  and  nodal  points 
of  union  of  the  spongioplasm.  The  fibres  of  the  latter  are  also  fre- 
quently arranged  in  a  radial  manner  for  a  short  distance  around  the 
centrosome.  But  in  many  instances  it  is  extremely  difficult  to  dis- 
tinguish the  centrosome,  and  its  constant  presence  in  cells  is  largely 
a  matter  of  inference.  Sometimes  the  centrosome  is  double,  the 
two  granules  lying  close  to  each  other  and  often  being  surrounded 
by  a  common  clear  zone  of  hyaloplasm. 

The  first  step  in  the  process  of  cell-division  by  the  indirect  method, 
or  karyokinesis,  is  a  division  of  the  centrosome  into  halves  (Fig. 
15),  which  separate  and  pass  to  opposite  points  in  the  cytoplasm. 
These  points  are  called  the  poles  of  the  cell,  and  when  the  new  cen- 


-( 


THE  CELL.  35 

trosomes  reach  them  they  are  called  the  polar  bodies.  In  these  situa- 
tions they  are  surrounded  by  a  more  distinct  zone  of  hyaloplasm 
than  that  which  enclosed  the  original  parent  centrosome,  and  beyond 
this  the  spongioplasm  is  frequently  arranged  in  radiations  of  unusu- 
ally thick  fibres.  The  polar  bodies  with  their  clear  envelopes  and 
the  prominent  radiations  about  them  are  collectively  known  as  the 
attraction -spheres  (Fig.  8). 

FIG.  8. 


Dividing  cell  from  ovum  of  ascaris  megalocephalus.  (Kostanecki  and  Siedlecki.)  a,  polar  body, 
centrosome,  surrounded  by  a  clear  zone ;  6,  chromosomes  of  the  dividing  nucleus.  Be- 
tween the  polar  bodies  is  the  achromatic  spindle,  and  radiating  from  each  attraction- 
sphere  are  delicate  filaments  of  spongioplasm.  The  cytoplasm  presents  indications  of 
vacuolation. 

While  the  polar  bodies  are  separating,  or  after  they  have  passed 
into  the  polar  regions  of  the  cell,  the  nucleus  begins  to  show  those 
changes  in  structure  which  constitute  karyokinesis.  This  process 
may  be  divided  into  a  number  of  phases,  as  follows : 

1.  The  Formation  of  the  Spirem  (Fig.  9). — This  consists  in  a  con- 
densation of  the  chromoplasm.  The  branches  of  the  nuclear  fila- 
ments are  withdrawn  into  the  substance  of  the  main  fibres,  into 
which  the  nuclear  membrane  or  peripheral  network  bounding  the 
nucleus  is  also  absorbed.  The  vesicular  character  of  the  nucleus  is 
lost  during  these  changes  in  the  arrangement  of  the  chromoplasm, 
which  appears  as  a  loose  tangle  or  skein  of  one  or  more  threads 
of  uniform  diameter  lying  freely  in  the  body  of  the  cell.  This 
skein  is  called  the  spirem.  The  chromoplasm  in  this  condensed  con- 
dition stains  more  deeply  with  nuclear  dyes  than  in  the  resting  con- 
dition of  the  nucleus.  The  nucleoli  in  the  meantime  become  faint 
and  seem  to  ultimately  disappear.  They  play  no  part  in  the  process 


36 


NORMAL  HISTOLOGY. 
FIG.  9.  FlG-  10- 


FIG.  11. 


FIG.  12. 


FIG.  14. 


FIG.  13. 


Diagrams  illustrating  the  phases  of  karyokinesis.    (Flemming.) 
Fig.  9.— Spirem. 
Fig.  10.— Monaster. 
Fig.  11.— Metakinesis,  early  stage. 
Fig.  12.— Metakinesis,  late  stage. 
Fig.  13.— Diaster. 
Fig.  14.— Dispirem. 

The  achromatic  spindle  is  represented,  but  not  the  centrosomes  (polar  bodies).    The  c 
body  is  also  omitted. 


THE  CELL. 


37 


of  cell-division,  unless  they  participate   in    the  formation  of  the 
achromatic  spindle. 

2.  The   Monaster  Phase  (Fig.  10). — The  threads  of  the  spirern 
suffer  a    rearrangement,  resulting  in  the   formation   of  a  sort  of 
wreath,  situated  midway  between  the  poles,  in  the  equatorial  plane, 
i.  e.}  the  plane    perpendicular  to  and   passing   through  the  centre 
of  a  line  joining  the  two  polar  bodies.     This  wreath  is  called  the 
monaster,  because  of   its  star-like   configuration   when  seen   from 
above.     When  viewed  in  profile  it  appears  as  a  band  of  fibres  lying 
in  the  equator.     It  is  at  first  made  up  of  a  single  thread  or  only  a 
few  threads,  but  subsequently  breaks  into  a  number  of  similar  frag- 
ments, called  chromosomes.     The  exact  number  of  these  varies  in 
different  species  of  animal,  but  is  constant  for  each  species  and  is 
always  divisible  by  two.     In  man  it  is  thought  to  be  sixteen. 

The  chromosomes  are  all  of  nearly,  if  not  quite,  the  same  size, 
and,  in  the  same  kind  of  cell,  closely  resemble  each  other  in  shape. 
The  most  common  form  appears  to  be  a  V-shaped  rod  lying  with 
its  angle  directed  toward  the  centre  of  the  wreath  or  monaster. 

3.  Metakinesis  (Figs.  11,  12,  16). — In  this  phase  of  karyokinesis 


FIG.  15. 


Karyokinetic  figures  in  epithelial  cells.  From  a  carcinoma  removed  by  operation.  (Lustig 

and  Galleotti.) 

Fig.  15.— The  centrosome  has  divided,  but  the  nucleus  is  still  in  the  resting  condition. 
Five  nucleoli  are  represented  within  the  nucleus. 

Fig.  16.— Metakinesis.    The  polar  bodies  have  divided. 

the  chromosomes  split  along  their  axes  into  two  exactly  equal  parts 
of  similar  shape,  and  these  halves  separate,  each  passing  toward 
one  of  the  attraction-spheres. 

Meanwhile,  the  structure  known  as  the  achromatic  spindle  has 
been  formed.  This  is  a  system  of  fibres  resembling  those  that  have 
already  been  described  as  radiating  from  the  polar  bodies,  but  of 
even  greater  prominence.  They  are  arranged  to  form  a  spindle 


38 


NORMAL  HISTOLOGY. 


with  its  apices  at  the  polar  bodies  and  its  equator  coincident  with 
that  of  the  cell  and  the  plane  of  the  monaster. 

It  is  along  the  lines  of  this  spindle  that  the  chromosomes  travel 
toward  the  centres  of  the  attraction-spheres  occupied  by  the  polar 
bodies. 

The  phases  of  karyokinesis  that  follow  metakinesis  are  similar  to 
those  that  preceded  it,  but  occur  in  inverse  order. 

4.  The    Diaster    Phase    (Fig.    13). — The    chromosomes,    having 
reached  the  attraction-spheres,  group  themselves  around  the  polar 
body  to  form  a  wreath  on  a  plane  perpendicular  to  the  axis  joining 
the  poles.     These  wreaths,  with  the  achromatic  spindle,  have  an 
appearance  somewhat  resembling  the  letter  H,  with  a  long  cross- 
piece,  formed  by  the  spindle,  remaining  uncolo^ed  or  only  faintly 
tinged  by  nuclear  dyes,  while  the  uprights,  made  up  of  the  chromo- 
somes, are  deeply  stained. 

The  ends  of  the  chromosomes  now  unite  to  form  a  thread,  and 
the  wreath-like  arrangement  gradually  passes  into  that  of  the 
dispirem. 

5.  Dispirem  (Figs.  14  and  17). — The  halves  of  the  original  chro- 
moplasm  of  the  nucleus  are  now  arranged  in  two  skeins  about  the 
poles.     From  these  the  two  daughter-nuclei  of  the  future  cells  are 
formed  (Fig.  18). 


FIG.  17. 


FIG.  18. 


Fig.  17.— Dispirem.    In  this  case  the  polar  bodies  have  not  divided  (compare  Fig.  16). 

Fig.  18.— Daughter-nuclei  which  have  nearly  reached  their  full  development.    Centrosomes 

present  in  the  cytoplasm. 
In  these  figures  the  structure  of  the  cytoplasm  is  not  given. 

During  metakinesis  the  cytoplasm  of  the  cell  begins  to  show 
signs  of  division.  This  may  be  accomplished  through  a  constric- 
tion of  the  body  of  the  cell,  which  gradually  becomes  deeper  and 
finally  severs  the  two  portions ;  or  a  series  of  punctiform  or  short 


THE  CELL.  39 

linear  enlargements  of  the  lines  of  the  achromatic  spindle  appear 
in  its  equator,  and  through  these  a  plane  of  cleavage,  dividing  the 
two  new  cells  from  each  other,  is  finally  established. 

It  is  rarely  that  any  biological  process  assumes  such  mathemat- 
ical precision  as  is  displayed  in  karyokinesis.  The  purpose  of  that 
mode  of  cell-division  appears  to  be  an  exactly  equal  partition  of 
all  parts  of  the  chromoplasm  between  the  young  cells.  Whether 
the  amount  of  cytoplasm  given  to  the  daughter-cells  is  the  same 
or  different,  the  division  of  the  chromoplasm  is  exactly  equal,  not 
only  in  its  whole  bulk,  but  each  chromosome,  which  appears  to  be 
the  morphological  unit  of  the  chromoplasm,  is  split  into  exactly 
equivalent  halves,  one  of  which  is  contributed  to  the  formation  of 
each  daughter-nucleus.  It  is  for  this  reason  that  the  chromoplasm 
is  looked  upon  as  the  carrier  of  hereditary  peculiarities. 

After  the  formation  of  the  daughter-nuclei,  the  centrosome 
usually  passes  from  it  into  the  cytoplasm.  It  may  divide  earlier 
than  has  been  described,  the  division  taking  place  while  it  exists 
as  the  polar  body,  or  even  earlier  (Fig.  16). 

A  cell  nearly  always  divides  to  form  two  new  cells,  but  some- 
times three  or  more  cells  may  be  produced,  the  chromosomes  being 
distributed  among  them  (Fig.  19).  Such  cases  are  probably 

FIG.  19. 


Epithelial  cell  from  a  carcinoma.  (Galeotti.)  The  centrosome  has  divided  into  four  portions, 
and  the  chromosomes  are  arranged  with  reference  to  these.  The  figure  represents  the  meta- 
kinetic  phase  of  karyokinesis,  which  will  result  in  the  formation  of  four  imperfect 
nuclei. 

always  morbid,  and  the  resulting  cells  are  not  wholly  the  equiv- 
alents of  the  parent  cell. 

It  occasionally  happens  that  the  cytoplasm  fails  to  divide  after 
the  formation  of  the  daughter-nuclei,  and  cells  with  two  or  more 
nuclei  result.  When  the  nuclei  continue  to  multiply  and  the 


40 


NORMAL  HISTOLOGY. 


cytoplasm  increases  in  amount,  but  does  not  suffer  division,  large 
multi  nucleated  cells  are  produced,  which  have  been  called  "  giant- 
cells."  They  occur  normally  in  the  marrow  of  bone  and  are  pro- 
duced in  many  of  the  inflammatory  processes. 

The  direct  or  amitotic  method  of  cell-division  is  inaugurated  by 
an  active  change  in  the  shape  of  the  nucleus,  which  may  have  pre- 
viously increased  in  size  and  become  richer  in  chromoplasm.  The 
nucleus  becomes  constricted  and  finally  separated  into  two  portions, 
which  are  not  necessarily  equally  rich  in  chromoplasm.  The  cyto- 
plasm, either  at  the  same  time  or  later,  becomes  similarly  con- 
stricted until  it  is  divided  into  two  parts,  each  containing  one  of 
the  nuclear  divisions  (Figs.  20,  21,  22). 


FTG.  20 


FIG.  21. 


FIG.  22. 


Amitotic  cell-division.    (Flemming.)    Epithelial  cells  from  the  bladder  of  a  salamander. 
Figs.  20  and  21  contain  nuclei  with  constrictions  dividing  them  into  nearly  equal  portions. 
Fig.  22.— Contiguous  cells,  each  containing  a  nucleus  about  half  the  size  of  those  prevailing 
in  the  tissue,  and,  therefore,  probably  the  result  of  cell-division  by  the  direct  process. 

It  is  believed  that  this  mode  of  division  does  not  result  in  the 
formation  of  cells  that  have  the  complete  character  of  the  parent- 
cell,  and  that  their  descendants  form  a  degenerate  race  that  is 
destined  to  extinction.  It  is  quite  obvious  that  no  such  precise 
partition  of  the  chromatic  substance  is  likely  to  take  place  as  that 
which  is  characteristic  of  karyokinesis,  and  if  the  chromosomes  are 
really  the  carriers  of  hereditary  peculiarities,  this  mode  of  division 
can  hardly  favor  their  perfect  transmission. 


CHAPTER   II. 
THE  ELEMENTARY  TISSUES. 

THE  various  parts  of  the  body  are  composed  of  a  small  number  of 
"  elementary  tissues."  Each  of  these  elementary  tissues  has  a  definite 
structure,  but  the  details  of  that  structure  may  vary  within  certain  lim- 
its in  different  parts  of  the  same  mass  or  in  different  situations  within 
the  body.  Such  variations  can  usually  be  referred  to  differences  in  the 
functional  activity  assigned  to  the  tissue,  which  is  not  always  exactly 
the  same  throughout  the  body.  For  example,  epithelium  is  an  ele- 
mentary tissue  consisting  of  cells  which  are  nearly  always  rich  in 
cytoplasm  and  are  separated  from  each  other  by  a  very  small  amount 
of  homogeneous  intercellular  substance.  Wherever  epithelium  is 
found  it  has  these  general  peculiarities  of  structure.  But  the  func- 
tions demanded  of  epithelium  are  of  widely  diverse  character  in 
different  situations,  and  its  structure  shows  a  corresponding  diversity 
in  its  details.  The  fact  that  it  is  made  up  almost  exclusively  of 
cells  leads  to  the  natural  inference  that  the  usefulness  of  epithelium 
depends  upon  cellular  activities.  Inasmuch  as  these  may  be  of 
very  different  character,  we  should  expect  the  tissue  to  vary  chiefly 
in  the  structure  and  arrangement  of  its  component  cells  according 
to  the  particular  activity  which  was  needed  and  the  manner  in 
which  it  was  utilized.  Such,  as  a  matter  of  fact,  is  the  case.  These 
considerations  will  be  made  clearer  if  we  follow  a  little  more  closely 
the  example  offered  by  epithelium. 

In  some  situations  epithelium  serves  to  protect  the  underlying 
tissues  from  injury.  But  the  usual  injurious  influences  which 
threaten  the  tissues  differ  in  different  parts  of  the  body,  and 
must,  therefore,  be  averted  by  different  means.  Upon  the  sur- 
face of  the  skin  they  are  chiefly  of  a  mechanical  or  chemical 
nature,  and  to  resist  them  the  cells  of  the  epithelium  forming  the 
epidermis  undergo  a  modification  in  structure,  resulting  in  the 
formation  of  a  superficial  horny  layer  which  is  highly  resistant  to 
abrasion  and  chemical  change.  Upon  the  inner  surfaces  of  the 

41 


42  NORMAL  HISTOLOGY. 

respiratory  passages  the  conditions  are  different.  Here  the  tissues 
require  protection  from  particles  of  dust  that  may  be  inhaled.  For 
this  purpose  the  epithelial  cells  lining  those  passages  are  provided 
with  minute,  hair-like  processes,  "cilia,"  which  execute  lashing  move- 
ments toward  the  outlets  of  the  passages  and  occasion  the  transpor- 
tation of  substances  coming  into  contact  with  them  toward  the 
outer  world.  In  the  digestive  tract  the  conditions  are  again  differ- 
ent. The  tissues  underlying  the  epithelial  lining  need  protec- 
tion from  the  chemical  action  of  the  fluids  in  the  stomach  and  intes- 
tine, as  well  as  from  friction  with  their  solid  contents.  The  cells 
of  the  epithelium  meet  these  needs  by  a  secretion  of  mucus,  which 
is  discharged  upon  the  inner  surfaces  of  the  digestive  organs,  where 
it  serves  as  a  protective  layer  and  as  a  lubricant, 

In  other  situations  epithelium  has  an  excretory  function,  which  is 
less  clearly  of  value  in  protecting  its  immediate  surroundings,  but 
is  essential  for  the  protection  of  the  whole  organism  from  substances 
which  would  exert  an  injurious  effect  if  they  were  permitted  to  ac- 
cumulate in  the  circulating  fluids  of  the  body.  These  substances 
are  absorbed  from  those  fluids  by  epithelial  cells,  from  which  they 
are  discharged  from  the  body  either  unchanged  or  after  transforma- 
tion into  other  chemical  compounds.  Here  the  most  obvious  prod- 
ucts of  cellular  activity  are  of  no  use  in  the  economy,  and  are  elim- 
inated from  it;  but  it  is  not  improbable  that  the  cells  which  separate 
them  or  their  antecedents  from  the  circulating  fluids  may  also 
discharge  useful  substances  into  those  fluids  ("  internal  secretion  "). 
We  must  not  assume  that  the  most  obvious  function  exercised  by  a 
tissue  is  the  only  service  it  does  to  the  organism. 

The  epithelium  which  carries  on  this  eliminative  function  is  nearly 
always  associated  with  other  elementary  tissues  to  form  an  organ, 
called  a  "gland,"  in  which  the  epithelium  is  the  functionally  active 
tissue,  the  other  tissues  being  subservient  to  it.  The  glands  of  the 
body  differ  considerably  in  both  structure  and  function,  but  in  all 
of  them  it  is  epithelium  which  elaborates  the  materials  essential  to 
the  formation  of  their  normal  secretions.  Mention  has  already 
been  made  of  those  glands  which  furnish  secretions  charged  with 
waste  materials  to  be  eliminated  from  the  body.  Such  glands  are 
called  excretory  glands,  and  are  exemplified  by  the  kidney.  Other 
glaiids,  distinguished  as  secretory  in  a  restricted  sense,  furnish  secre- 
tions which  are  of  service  to  the  organism.  Examples  of  such 
glands  are  those  which  discharge  their  secretions  into  the  alimentary 


THE  ELEMENTARY  TISSUES.  43 

tract  where,  by  virtue  of  the  ferments  they  contain,  they  prepare 
the  food  for  absorption.  Another  example  of  a  secretory  gland  is 
furnished  by  the  sebaceous  glands  of  the  skin,  which  produce  an 
oily  substance  serving  to  keep  the  epidermis  upon  which  it  is 
discharged  soft  and  pliable. 

In  the  secretory  glands  the  cells  of  the  functional  epithelium 
elaborate  within  their  bodies  the  substances  necessary  to  give  the 
glandular  secretion  its  peculiar  and  useful  characters.  These  sub- 
stances accumulate  within  the  cells,  where  they  are  stored  until 
required,  when  they  are  discharged  into  the  secretion.  While  in 
the  stored  condition  within  the  cells  these  substances  may  have  a 
different  chemical  constitution  from  that  which  they  acquire  when 
they  are  discharged  from  the  cells.  A  simple  example  of  this 
chemical  transformation  is  furnished  by  the  liver,  in  the  epithelial 
cells  of  Avhich  carbohydrates  are  stored  as  glycogen,  to  be  liberated 
as  a  closely  related  chemical  substance,  glucose.  In  like  manner 
the  ferments  stored  in  the  epithelial  cells  of  the  digestive  glands 
are  not  fully  formed  while  in  that  situation,  but  exist  in  states 
known  as  "  zymogens,"  from  which  the  potent  ferment  appears  to 
be  readily  formed  when  the  cells  are  called  upon  to  furnish  it. 

It  is  apparent,  then,  that  the  elementary  tissue,  epithelium,  can- 
not have  the  same  microscopical  structure  in  all  the  situations  in 
which  it  is  found  ;  but,  notwithstanding  these  variations,  wherever 
epithelium  occurs  it  presents  certain  general  structural  peculiarities 
which  are  constant  and  which  distinguish  it  from  the  other  element- 
ary tissues.  Similarly,  each  of  the  other  elementary  tissues  pre- 
sents variations  in  the  details  of  its  structure  in  different  situations, 
but  always  retains  certain  general  structural  characteristics  dis- 
tinguishing it  from  all  the  other  elementary  tissues.  It  is  the  first 
task  of  the  student  of  histology  to  learn  to  recognize  and  identify 
these  elementary  tissues  wherever  they  occur  and  however  they  may 
vary  from  the  type  which  is  first  presented  to  him  for  study. 

In  the  following  chapters  an  attempt  is  made  to  give  the  student 
an  idea  of  the  essential  structure  of  the  elementary  tissues,  so  that 
he  may  recognize  them  in  specimens  which  he  examines  with  the 
microscope.  For  this  purpose  they  have  been  arranged  in  the 
order  of  their  structural  simplicity. 

When  examining  a  specimen  under  the  microscope  with  a  vi£w 
to  recognizing  the  elementary  tissues  it  contains,  the  student  should 
habitually  ask  himself  the  following  questions :  (1)  What  are  the 


44  NORMAL  HISTOLOGY. 

general  characters  of  the  cells  entering  into  the  structure  of  the 
tissue  ?  (2)  What  kind  of  intercellular  substances  separates  those 
cells  ?  (3)  How  are  the  cells  arranged  with  reference  to  each  other 
and  the  intercellular  substances  ?  Correct  answers  to  these  three 
questions  will  enable  him  to  quickly  determine  the  nature  of  the 
tissue  he  is  observing,  even  if  it  should  vary  considerably  in  struct- 
ural details  from  examples  of  the  same  tissue  with  which  he  has 
already  become  familiar. 


CHAPTER   III. 
THE  EPITHELIAL   TISSUES.1 

I.  ENDOTHELIUM. 

General  Characters. — (1)  The  cells  possess  thin  membranous  bodies, 
except  at  the  site  of  the  nucleus,  to  enclose  which  the  cell-body  is 
thickened.  (2)  The  intercellular  substance  is  minimal  in  amount ; 
clear  and  homogeneous  in  character.  (3)  The  cells  are  arranged, 
edge  to  edge,  in  a  single  layer.  The  wavy  or  denticulate  edges  of 
neighboring  cells  fit  into  each  other,  being  separated  by  a  mere  line 
of  the  intercellular  substance  which  in  this  tissue  has  received  the 
name  of  "  cement-substance  "  (Fig.  23). 

Endothelium  forms  a  thin  membranous  tissue  composed  almost 
exclusively  of  cells.  It  occurs  in  its  most  isolated  form  in  the  cap- 
illary bloodvessels,  the  walls  of  which  are  simply  tubes  of  endo- 
thelinm,  supported  externally  by  the  surrounding  tissues  and  fluids 
and  internally  by  the  enclosed  blood.  It  also  covers  the  tissues 
surrounding  the  serous  cavities  of  the  body,  where  it  serves  both  as 
a  lining  to  the  cavities  and  a  smooth  covering  to  the  organs,  dimin- 
ishing the  friction  resulting  from  their  movements  against  each 
other.  It  does  not  occur  in  any  situation  where  it  would  be  exposed 
directly  to  the  external  world. 

The  cells  of  endothelium  vary  somewhat  in  size  and  shape.  They 
may  be  polygonal,  diamond,  or  stellate  in  form,  and  during  life  are 
soft  and  extensible  so  that  their  sizes  may  be  modified  by  stretching 
or  tension  in  one  or  more  directions.  The  cell-bodies,  or  cytoplasm, 
are  usually  clear  and  apparently  structureless  or  only  slightly  granu- 
lar, but  occasionally  some  of  the  cells  are  smaller  and  more  granular 
than  the  majority.  This  is  especially  marked  in  the  cells  surround- 
ing minute  apertures  that  are  found  here  and  there  in  the  endo- 

1  The  term  "epithelial"  is  used  here  in  its  most  inclusive  sense  to  designate 
those  tissues  which  cover  surfaces,  whether  those  surfaces  are  exposed  to  the  outer 
world,  as,  for  example,  the  skin  and  the  mucous  membranes,  or  are  wholly  enclosed, 
as  are  the  inner  surfaces  of  the  bloodvessels,  lymphatics,  and  serous  surfaces. 

45 


46  NORMAL  HISTOLOGY. 

thelial  lining  of  the  serous  cavities  (Fig.  24).  These  openings  are 
called  stomata  and  furnish  a  direct  communication  between  the  se- 
rous cavities  and  the  lymphatic  spaces  in  the  tissues  surrounding 
them.  These  openings  virtually  convert  the  serous  cavities  into 
enormous  lymph-spaces  forming  a  part  of  the  general  lymphatic 
system. 

FIG.  23. 


Mesentery  of  frog  treated  with  silver  nitrate.  The  mesentery  is  covered  on  both  surfaces 
with  a  layer  of  endothelium.  Between  these  is  areolar  connective  tissue  containing 
bloodvessels,  lymphatics,  and  nerves.  In  this  figure  only  the  two  endothelial  layers  and 
a  capillary  bloodvessel  are  represented :  a,  nucleus  of  endothelial  cell  belonging  to  upper- 
most layer ;  6,  nucleus  of  cell  belonging  to  deep  layer  forming  the  lower  surface  of  the 
specimen;  c,  intercellular  cement  between  cells  of  upper  layer  of  endothelium  ;  d,  d, 
nuclei  of  endothelial  cells,  forming  a  capillary  bloodvessel,  seen  in  profile.  The  bodies  of 
these  cells  are  not  reproduced  in  the  figure.  The  cement  in  the  deep  layer  of  endothe- 
lium is  represented  by  finer  lines  to  distinguish  it  from  that  belonging  to  the  upper  layer. 

The  edges  of  contiguous  endothelial  cells  are  not  everywhere  in 
equally  close  approximation  to  each  other  (Fig.  25).  The  occasional 
points  where  they  are  more  widely  separated  than  usual  are  occu- 
pied either  by  an  increased  amount  of  the  cement-substance,  or  pro- 
cesses from  cells  in  the  underlying  tissues  are  here  intercalated 
between  the  endothelial  cells,  reaching  the  surface  of  the  serous 
membrane.  In  either  case  these  points  of  separation  of  the  endo- 
thelial cells  are  not  openings  through  the  tissue,  though,  as  we  shall 
see  in  a  subsequent  chapter,  they  are  spots  where  the  tissue  is  rela- 


THE  EPITHELIAL   TISSUES. 


47 


tively  more  pervious  than  elsewhere.   They  are  called  pseudostomata, 
to  distinguish  them  from  the  stomata  already  mentioned. 

FIG.  24. 


Endothelium  on  a  serous  surface  of  the  frog.  (Klein.)  a,  stoma  bounded  by  endothelial  cells 
with  granular  cytoplasm;  b,  pseudostoma.    The  nuclei  of  the  cells  are  not  represented. 

The  intercellular  substance  in  endothelium  is  so  small  in  amount 
and   so  homogeneous  and  transparent  that  it  escapes  observation 

FIG.  25. 


Endothelial  lining  of  a  small  vein  treated  with  silver  nitrate  ;  dog.  (Engelmann.)  The  fig- 
ure represents  a  tube  formed  of  endothelium  the  cells  of  which  vary  in  size  and  shape. 
The  whole  wall  of  a  capillary  has  essentially  the  same  structure  as  this  venous  lining( 
but  its  calibre  is  smaller.  The  upper  branch  in  this  figure  may  represent  a  capillary 
opening  into  the  vein,  a,  a,  pseudostomata  occupied  by  cement-substance. 

under  the  microscope  unless  special  means  are  employed  for  its  dem- 
onstration.    The  simplest  of  these  consists  in  treating  the  fresh 


48  NORMAL  HISTOLOGY. 

tissue  with  a  1  per  cent,  solution  of  nitrate  of  silver  for  a  few  mo- 
ments, washing  with  distilled  water,  and  then  exposing  it  to  the 
rays  of  the  sun.  During  this  treatment  the  intercellular  substance 
enters  into  combination  with  the  silver.  Upon  exposure  to  strong 
light  this  compound  is  destroyed,  leaving  an  insoluble  black  precipi- 
tate of  silver  oxide.  When  the  specimen  is  examined  under  the 
microscope,  the  site  of  the  cement-substance  is  marked  by  the 
presence  of  this  precipitate.  Endothelium  so  treated  shows  a  net- 
work of  fine  dark  lines,  the  meshes  of  which  are  occupied  by  the 
cells  of  the  tissue.  When  no  such  method  has  been  employed  to 
render  the  intercellular  substance  conspicuous,  the  outlines  of  the 
cells  cannot  be  distinguished,  and  the  tissue  appears  as  a  continuous, 
nearly  homogeneous  membrane  containing  nuclei  at  more  or  less 
regular  intervals.  When  seen  in  profile  or  vertical  section,  endo- 
thelium  appears  as  a  delicate  line,  expanded  at  intervals  to  enclose  a 
nucleus  (Fig.  26).  The  nuclei  of  the  endothelial  cells  are  round  or 


Diagram  of  vertical  section  through  a  serous  membrane  :  a,  nucleus  of  endothelial  cell :  bt 
body  of  cell ;  c,  line  of  junction  between  two  cells  occupied  by  cement-substance  ;  d,  pro- 
cess of  connective-tissue  cell  occupying  a  portion  of  the  intercellular  space  between  two 
endothelial  cells,  one  variety  of  pseudostoma ;  e,  areolar  tissue  with  fusiform  and  stel- 
late cells.  The  vessels  and  nerves  in  the  areolar  tissue  have  been  omitted. 

oval,  and  each  cell  usually  possesses  but  a  single  nucleus  situated 
near  its  centre,  but  occasionally  cells  with  two  nuclei  are  observed. 
Functionally,  endothelium  appears  to  play  only  a  passive  role  in 
most  situations  in  which  it  is  found.  It  furnishes  a  smooth  cover- 
ing for  those  internal  surfaces  of  the  body  which  are  exposed  to 
friction,  as,  for  example,  in  the  serous  cavities  and  the  inner  sur- 
faces of  the  vascular  systems.  In  the  capillary  bloodvessels  and 
lymphatics  endothelium  forms  the  entire  wall  of  the  vessels,  and 
its  thinness  permits  the  passage  of  fluids  through  those  walls.  The 
fact  that  the  lymph  in  different  parts  of  the  body  varies  somewhat 


THE  EPITHELIAL   TISSUES.  49 

in  composition  has  led  to  the  inference  that  the  endothelium  of  the 
capillary  walls  exercises  an  active  function  in  determining  what 
shall  pass  through  it ;  that  the  lymph  is  a  sort  of  endothelial  secre- 
tion. It  is  difficult,  however,  to  reconcile  this  view  with  the  fact 
that  the  endothelial  cells  are  so  poor  in  cytoplasm. 
Endothelium  is  developed  from  the  mesoderm. 

II.  EPITHELIUM. 

General  Characters. — (1)  The  cells  are  nearly  always  large  and 
rich  in  granular  cytoplasm.  They  contain  distinct  round  or  oval, 
vesicular  nuclei,  of  which  there  is  usually  only  one  in  each  cell. 
(2)  The  intercellular  substance  is  very  small  in  amount  and  is  clear 
and  homogeneous.  (3)  The  arrangement  of  the  cells  and  their  size 
and  shape  all  vary  greatly,  giving  rise  to  a  number  of  varieties  of 
epithelium,  which  are  classified  according  to  the  shape  and  arrange- 
ment of  the  cells.  In  pavement-epithelium  the  cells  are  thin  and 
arranged  in  a  single  layer,  not  unlike  endothelium.  In  cubical 
epithelium  the  cells  are  thicker  and  also  usually  arranged  in  but  a 
single  layer.  In  columnar  epithelium  the  cells  are  prismatic  in  form 
and  rest  with  their  bases  upon  the  surface  of  the  tissues  beneath. 
They  are  usually  separated  at  their  bases  by  pyramidal  cells,  so 
that  the  layer  of  epithelium  cannot  be  said  to  consist  strictly  of  but 
one  layer  of  cells,  and  in  some  situations  there  are  several  distinct 
layers.  In  stratified  epithelium  the  cells  are  superimposed  upon 
each  other  to  form  a  layer  of  cells,  the  thickness  of  which  is  several 
times  the  diameter  of  a  single  cell.  The  cells  of  the  variety  of  epi- 
thelium called  ciliated  epithelium  differ  from  those  of  the  other 
varieties  in  possessing  delicate,  hair-like  processes  which  project 
from  the  free  surface  of  the  tissue. 

Epithelium  resembles  endothelium  in  being  composed  almost 
exclusively  of  cells  separated  by  a  minimal  amount  of  intercellular 
substance.  Like  endothelium,  it  is  nearly  always  found  covering 
other  tissues  and  having  one  free  surface.  The  two  tissues  differ 
greatly  in  the  character  of  their  cells,  with  one  notable  exception. 
This  exception  is  found  in  the  epithelial  lining  of  the  pulmonary 
alveoli,  where  the  pavement-epithelium  contains  cells  that  closely 
resemble  those  of  endothelium.  These  cells  are,  however,  directly 
exposed  to  the  inspired  air,  while  endothelium  is  only  found  in  situa- 
tions where  it  is  protected  from  all  contact  with  the  external  world. 

1.  Cubical  Epithelium. — The  cells   of  this  variety  of  epithelium 


50 


NORMAL  HISTOLOGY. 


are  approximately  of  the  same  diameter  in  all  directions.  They 
may  be  almost  strictly  cubical  or  spherical,  but  are  usually  polyhed- 
ral as  the  result  of  mutual  compression,  their  contiguous  surfaces 
being  flattened.  They  are  usually  disposed  in  a  single  layer  upon 
a  surface  furnished  by  the  underlying  tissues,  as,  for  example,  in 
tubular  or  racemose  glands,  but  they  may  be  aggregated  to  form  a 
solid  mass  of  cells  filling  a  sac,  as  in  the  sebaceous  glands  of  the 
skin,  or  in  strands  or  columns,  variously  disposed,  as  in  the  liver 
and  suprarenal  bodies. 

It  is  this  form  of  epithelium  that  is  chiefly  concerned  in  perform- 
ing the  functions  of  secretion,  and,  for  this  reason,  it  is  frequently 
designated  as  "  glandular  epithelium." 

The  appearance  of  the  individual  cells  varies  considerably  accord- 
ing to  the  functions  that  they  perform  and  the  stage  of  functional 
activity  which  obtained  at  the  time  cellular  changes  were  arrested 
Avhen  the  particular  specimen  was  prepared  for  study.  It  will  suf- 
fice for  present  purposes  of  description  to  call  attention  to  the  fact 
that  the  cytoplasm  is  usually  highly  granular,  partly  because  of  its 
own  structure,  partly  because  many  of  the  substances  elabo- 
rated and  stored  within  the  cells  as  the  result  of  their  functions 
appear  in  the  form  of  granules  (metaplasm).  The  nature  of  these 
granules  varies.  They  may  be  albuminoid,  zymogenic  granules,  or 
minute  drops  of  fatty  substances,  which  may  coalesce  to  form  dis- 
tinct oily  globules,  or  they  may  consist  of  carbohydrates,  e.  g.,  gly- 
.cogen.  The  granular  condition  of  the  cytoplasm  may  be  so  marked 


FIG.  27. 


FIG.  28. 


IBlP 


Cubical  epithelium. 


FIG.  29. 


Fig.  27.— Six  cells  from  the  sublingual  gland  of  a  man  who  was  executed.    (Schiefferdecker.) 
Fig.  28.— Three  isolated  cells  from  the  gastric  tubules  of  the  dog  and  cat.    (Trinkler.) 
Fig.  29.— Cell  with  highly  granular  cytoplasm,  the  result  of  stored  metaplasm,  chiefly  gly- 
cogen.    (Barfurth.) 

as  to  render  the  detection  of  the  nucleus  difficult  in  unstained  speci- 
mens (Figs.  27,  28,  and  29). 

In  this  form  of  epithelium  the  presence  of  two  nuclei  in  a  single 
cell  is  more  frequent  than  in  the  other  varieties. 


THE  EPITHELIAL   TISSUES. 


51 


2.  Pavement-epithelium. — This  variety  of  epithelium  consists  of 
thin  cells  arranged  edge  to  edge  to  form  a  single  layer.  With  the 
exception  of  certain  regions  on  the  surfaces  of  the  pulmonary 
alveoli,  the  cells  are  more  cytoplasmic  and  granular  than  are  those 
of  endothelium  which  this  tissue  in  other  respects  closely  resembles. 
During  foetal  life  the  smaller  air-passages  and  alveoli  of  the  lung 
are  lined  by  a  pavement-epithelium,  the  cells  of  which  are  nearly 
as  thick  as  those  of  some  varieties  of  cubical  epithelium.  When, 
however,  the  lung  is  expanded  by  the  respiratory  acts  following 
birth,  many  of  the  cells  lining  the  alveoli  become  greatly  extended 
and  flattened  until  their  bodies  are  thin  and  membranous  and  their 
nuclei  inconspicuous  or  even  destroyed  (Fig.  30).  These  greatly 
flattened  epithelial  cells  are  found  covering  those  portions  of  the 

FIG.  30. 


~s^-    - 

Pavement-epithelium.  Surface  view  of  the  lining  of  a  pulmonary  alveolus  ;  man.  (Kolliker.) 
a,  membranous  cell  without  a  nucleus ;  6,  nucleated  granular  cell ;  c,  cut  surface  of  the 
vertical  wall  of  the  alveolus,  the  structure  of  which  is  not  represented. 

alveolar  walls  in  which  the  capillary  bloodvessels  are  situated  and 
permit  a  ready  interchange  of  gases  between  the  air  in  the  alveolar 
cavities  and  the  blood  circulating  in  their  walls.  Many  of  the 
epithelial  cells  covering  the  tissues  in  the  meshes  between  the 
capillaries  retain  the  cytoplasmic  and  granular  character  possessed 
before  birth  and  appear  capable  of  multiplying  and,  perhaps, 
replacing  such  of  the  thinner  cells  as  may  be  thrown  off  or 
destroyed. 

It  will  be  evident,  from  the   foregoing  descriptions,  that  there 


52 


NORMAL  HISTOLOGY. 


is  no  sharp  structural  line  separating  cubical  from  pavement-epithe- 
lium. Functionally,  pavement-epithelium  is  a  much  less  active 
tissue  than  the  cubical  variety. 

3.  Columnar  Epithelium  (Figs.  31,  32,  33). — The   cells  of  this 


FIG.  31. 


Columnar  epithelium.  From  tongue  of  pseudopus.  (Seiler.)  a,  three  cells  with  intact  cyto- 
plasm, except  the  central  one,  which  contains  a  vacuole ;  6,  three  cells  of  which  the  dis- 
tal ends  contain  drops  of  fluid  (vacuoles)  or  of  metaplasm. 

form  of  epithelium  are  of  a  general  columnar  or  prismatic  shape 
and  possess  a  single  nucleus  and  a  cytoplasm  that  is  usually  dis- 
tinctly granular.  They  are  arranged  with  their  long  axes  parallel 
to  each  other,  so  that  their  free  ends  form  the  surface  of  the  epithe- 


FIG.  32. 


FIG.  33. 


Columnar  epithelium. 
Fig.  32.— From  small  intestine  of  the  mouse.  (Paneth.)  a,  pyramidal  reserve  cell,  nucleus  not 

included  in  section ;  b,  "goblet"  cell,  enclosing  a  large  drop  of  secretion. 
Fig.  33. — From  small  intestine  of  the  mouse.    (Paneth.)    Columnar  epithelial  cells  seen  from 

above  :  b,  goblet-cell,  the  mucous  contents  darkened  by  the  hardening  process ;  s,  s,  highly 

granular  cells  which  have  recently  discharged  their  secretion. 

lium,  while  their  deeper  ends  either  rest  upon  the  tissues  beneath 
the  epithelium  or  upon  other  epithelial  cells  of  diiferent  shape 
which  form  one  or  more  layers  between  the  columnar  cells  and  the 
underlying  tissues.  When  they  rest  directly  upon  the  tissues 
beneath  there  are  usually  other  epithelial  cells  of  a  pyramidal  or 
oval  shape  which  may  be  regarded  as  immature  cells  ready  to  take 
the  place  of  such  fully  developed  cells  as  may  become  detached  or 
destroyed.  The  presence  of  these  cells  occasions  a  narrowing  of 


THE  EPITHELIAL   TISSUES. 


53 


the  deep  ends  of  the  columnar  cells,  so  that  they  are  not  strictly 
prismatic  in  form.  In  cross-section,  or  when  viewed  in  a  direction 
parallel  to  their  long  axes,  the  cells  have  a  polygonal  form  due  to 
the  lateral  pressure  they  exert  upon  each  other  (Fig.  33). 

The  nuclei  of  the  columnar  cells  are  oval,  situated  nearer  the 
base  of  the  cell  than  its  superficial  end  with  their  long  axes  parallel 
to  those  of  the  cells  themselves,  and  are  vesicular  in  structure  with 
a  distinctly  reticular  arrangement  of  the  chromatin  filaments. 

Columnar  epithelium  is  found  chiefly  upon  the  free  surfaces  of 
mucous  membranes,  but  also  occurs  in  some  of  the  secreting  glands. 
The  minute  structure  of  the  cells  varies  somewhat  in  different  situ- 
ations, but  the  consideration  of  these  minutiae  must  be  deferred 
until  a  description  of  the  structure  of  the  different  organs  is  under- 
taken in  a  subsequent  chapter. 

4.  Ciliated  Epithelium  (Figs.  34,   35,   36).— Ciliated  epithelium 


FIG.  34. 


Fro.  35. 


FIG.  36. 


Ciliated  epithelium.    (Frenzel.) 

Fig.  34.— Cubical  cells  with  long  cilia  (hb).  The  nuclei  of  the  cells  are  obscured  by  the  gran- 
ular cytoplasm. 

Fig.  35.— Columnar  cells.    The  rodded  margin,  fs,  corresponds  to  the  cuticle  in  Fig.  37. 

Fig.  36— Diagram  illustrating  variations  in  the  structure  of  the  ciliated  ends  of  cells.  The 
rodded  portion,  ok  to  nk,  corresponds  to  the  cuticle  of  other  varieties  of  epithelium, 
though  the  latter  do  not  possess  the  knobbed  ends  of  the  rods  represented  in  this  figure ; 
hb,  cilia. 

is  merely  a  variety  of  either  columnar  or  cubical  epithelium  in 
which  the  free  ends  of  the  cells  are  beset  with  delicate  hair-like 
processes,  which  execute  lashing  movements  in  some  one  direction. 
It  is  found  lining  the  trachea  and  bronchi,  the  cilia  here  serving  to 
propel  toward  the  larynx  such  particles  of  dust  as  are  brought  into 
the  respiratory  passages  by  the  currents  of  air  during  respiration. 
Ciliated  epithelium  also  occurs  on  the  lining  membranes  of  the  nose 


54  NORMAL  HISTOLOGY. 

and  the  adjoining  bony  cavities,  the  mucous  membrane  of  the  uterus 
and  the  Fallopian  tubes,  the  vasa  efferentia  of  the  testis  and  a  part 
of  the  epididymus,  the  ventricles  of  the  brain  (except  the  fifth),  the 
central  canal  of  the  spinal  cord,  and  the  ducts  of  some  glands. 

The  possession  of  cilia,  which  are  very  motile  organs,  presents 
a  marked  departure  in  specialization  from  the  usual  metabolic  func- 
tions of  epithelium.  Ciliated  epithelium  rarely  exercises  a  secretory 
function,  its  stock  of  energy  being  utilized  to  produce  motion  instead 
of  chemical  change.  But  there  are  secreting  varieties  of  epithelium 
possessing  a  "  cuticle  "  which  appears  to  be  morphologically  anal- 
ogous to  the  cilia,  but  in  which  the  fibrils  are  less  highly  developed, 
probably  not  motile,  and,  therefore,  functionally  not  the  equiva- 

FJG.  37. 


Cuticularized  epithelium,  intestine  of  dog.  (Paneth.)  Rodded  cuticle  of  the  free  ends  of 
columnar  cells.  In  most  specimens  of  ciliated  epithelium  from  human  tissues,  where  no 
special  care  has  been  taken  to  preserve  the  cilia,  the  ciliated  border  presents  the  appear- 
ances shown  in  Fig.  37. 

lents  of  cilia.  This  cuticle  is  highly  developed  in  the  cells  cover- 
ing the  mucous  membrane  of  the  intestine  (Fig.  37). 

5.  Stratified  Epithelium. — In  the  varieties  of  epithelium  hitherto 
considered  the  cells  are,  in  the  main,  disposed  upon  some  surface 
in  a  single  layer,  some,  at  least,  of  the  cells  usually  extending  from 
the  bottom  of  the  layer  to  its  surface. 

Stratified  epithelium  is  distinguished  from  these  by  being  of 
greater  depth  and  consisting  of  several  layers  of  cells.  The  epithe- 
lium lining  the  cheek  or  the  oesophagus  may  be  taken  as  a  typical 
example  of  this  variety. 

The  most  deeply  situated  cells  are  small  and  nearly  filled  by  the 
round  or  oval  nucleus.  They  undergo  frequent  division,  and  as 
they  multiply  some  of  them  are  crowded  toward  the  surface.  For 
a  time  these  increase  in  size  through  a  growth  of  their  cytoplasm. 
But  as  they  are  pushed  nearer  to  the  surface  and  farther  from  the 
sources  of  nutrition  in  the  vascular  tissues  underlying  the  epithe- 
lium, they  become  flattened  and  their  bodies  lose  their  cytoplasmic 
character,  being  converted  into  a  dry,  horny  substance,  keratin. 


THE  EPITHELIAL   TISSUES. 


55 


Upon  the  free  surface  they  are  reduced  to  thin  scales,  closely 
adhering  to  each  other  and  their  subjacent  neighbors,  but  entirely 
devoid  of  both  cytoplasm  and  nucleus  (Fig.  38). 

Stratified  epithelium  is  found  upon  surfaces  exposed  to  friction, 
which  it  serves  to  protect  against  mechanical  injury,  and,  in  some 


FIG.  38. 


Stratified  epithelium,  oesophagus  of  the  rabbit:  a,  karyokinetic  figure  in  a  cell  of  the  deep 
layer,  demonstrating  the  fact  that  the  cells  multiply  in  this  region ;  b,  larger  flattened 
cell  nearer  the  surface ;  c,  horny  layer  made  up  of  cells  that  have  undergone  keratoid 
degeneration  ;  d,  underlying  fibrous  tissue.  In  one  place,  near  the  centre  of  the  figure, 
six  blood-corpuscles  reveal  the  presence  of  a  small  vessel ;  e,  tangential  section  of  a  small 
fibrous  papilla  extending  into  the  epithelium  and  surrounded  by  young  epithelial  cells. 

cases,  against  desiccation.  It  forms  the  epidermis  of  the  skin, 
and  lines  the  mouth,  oesophagus,  rectum,  and  vagina.  In  these  situ- 
ations the  scaly  or  squamous  cells  of  the  surface  are  constantly 
being  removed  by  the  attrition  to  which  they  are  exposed,  but  are 
as  constantly  replaced  by  fresh  cells  from  the  deeper  layers  of  the 
epithelium.  Pressure  and  moderate  friction  stimulate  the  multi- 
plication of  the  cells  in  the  deepest  layers  of  the  tissue,  so  that 
parts,  e.  g.  of  the  skin  which  are  especially  subjected  to  such  influ- 
ences acquire  a  thicker  epidermis  (callus). 

Where  the  stratified  epithelium  consists  of  many  layers  of  cells, 
as  is  the  case,  for  instance,  upon  the  skin,  there  is  a  provision  for 
the  nourishment  of  the  growing  cells  which  are  somewhat  removed 
from  the  vascularized  subjacent  tissues.  The  cells  of  the  deeper 
layers  are  somewhat  separated  from  each  other,  leaving  a  space 
between  them  through  which  nutrient  fluids  can  circulate.  Across 
this  space  numerous  minute  projections  or  "  prickles,"  springing 
from  neighboring  cells,  join  each  other,  forming  connecting  bridges 
between  the  cells.  When  isolated,  such  cells  appear  covered  with 
these  small  spicules  ("  prickle-cells  "),  and  their  presence  probably 


56  NORMAL  HISTOLOGY. 

increases  the  tenacity  with  which  the  cell-remains  adhere  to  each 
other  when  they  become  hardened  and  toughened  on  the  surface  of 
the  epithelial  layer  (Fig.  39). 

These  delicate  bridges  connecting  neighboring  cells  are  not  pecu- 
liar to  stratified  epithelium,  though  they  are  more  conspicuous  in 
that  tissue  than  elsewhere.  They  have  been  observed  between  the 
cells  of  the  columnar  epithelium  of  the  intestinal  mucous  mem- 
brane, and  also  between  the  cells  of  other  elementary  tissues ;  e.  g., 
smooth  muscular  tissue. 

6.  Transitional  Epithelium  (Figs.  40  and  41). — This  variety  re- 
sembles stratified  epithelium  in  forming  layers  several  cells  in  thick- 


Prickle  cells  from  human  stratified  epithelium.  (Rabl.)  Four  cells  with  delicate  processes  unit- 
ing across  an  intervening  space  are  represented.  The  lower  right-hand  cell  is  just  below 
the  upper  surface  of  the  section,  so  that  its  surface  is  seen.  This  is  covered  with  minute 
spots,  which  are  end  views  of  the  prickles  directed  toward  the  observer.  The  nucleus 
of  this  cell  is  not  in  sharp  focus,  a  fact  indicated  by  the  fainter  outline  in  the  figure. 

ness,  but  differs  in  the  character  of  its  superficial  cells.  These  do  not 
undergo  the  horny  change  peculiar  to  stratified  epithelium,  but  con- 
tinue to  increase  in  size,  forming  a  covering  of  very  large  cells  lying 
upon  those  beneath.  Under  these  largest  superficial  cells  are  pyri- 
form  cells  lying  with  their  larger,  rounded  ends  next  to  the  topmost 
layer,  while  their  deeper  and  more  attenuated  ends  lie  between  the 
oval  or  round  cells  that  form  the  one  or  two  deepest  layers  of  the 
epithelium  and  rest  upon  the  underlying  tissues. 

Transitional  epithelium  is  found  lining  the  renal  pelves,  ureters, 
and  bladder.  Its  structure  permits  of  a  considerable  stretching  of 
the  tissues  beneath  without  rupture  of  the  epithelial  layer  over 
them,  the  cells  of  which  become  flattened  to  cover  the  increased 
surface,  to  return  to  their  first  condition  when  the  viscus  which  they 
line  is  emptied.  This  is  notably  the  case  in  the  bladder,  the  epi- 


THE  EPITHELIAL  TISSUES. 


57 


thelial   lining  of  which  may  be  taken  as  a  type  of  this  variety  of 
tissue. 

The  functional  activities  of  epithelium  are  in  marked  contrast  to 
the  comparatively  inert  character  of  endothelium.    The  cytoplasmic 

FIG.  40. 


Transitional  epithelium  from  bladder  of  the  mouse.  (Dogiel.)  1, 2, 3,  and  U  indicate  the  layers 
of  cells,  not  everywhere  equally  well  defined,  a,  hyaloplasmic  surface,  and,  6,  cyto- 
plasmic body  of  large  superficial  cell ;  c,  leucocyte — i.  e.,  white  blood-corpuscle  that  has 
wandered  into  the  epithelium  by  virtue  of  its  amoeboid  movements  ;  d,  karyokinetic 
figure  in  a  cell  belonging  to  the  deepest  layer.  Beneath  this  layer  is  the  fibrous  tissue, 
which  is  covered  by  the  epithelium  and  forms  a  part  of  the  wall  of  the  bladder.  The 
superficial  cell,  which  is  fully  represented,  contains  two  nuclei,  a  not  very  infrequent 
occurrence  in  these  cells. 

nature  of  the  epithelial  cell,  when  contrasted  with  the  poverty  in 
cytoplasm  of  the  cell  in  endothelium,  would  lead  us  to  expect  this 
difference  in  the  cellular  activities  of  the  two  tissues.  At  the  begin- 
ning of  this  chapter  a  sketch  of  the  manifold  functions  of  epithe- 

FIG.  41. 


Transitional  epithelium.    Isolated  cells  from  the  bladder  of  the  frog.    (List.) 

Hum  was  given.  It  is  a  fair  general  statement  of  its  usefulness  to 
say  that  epithelium  is  chiefly  concerned  in  bringing  about  chemical 
changes  in  substances  brought  to  it.  Sometimes  these  substances 
are  elaborated  into  fresh  cell-constituents,  and  the  activity  of  the 


58  NORMAL  HISTOLOGY. 

tissue  is  displayed  chiefly  in  an  active  multiplication  and  growth  of 
its  cells.  This  is  especially  true  in  the  stratified  variety,  where  pro- 
tection is  provided  by  a  constantly  renewed  supply  of  cells.  In 
other  cases  the  substances  received  by  the  cells  are  elaborated  into 
definite  compounds  destined  to  form  the  essential  constituents  of  a 
secretion.  This  secretory  function  of  epithelium  is  an  extremely 
important  one,  and  for  its  performance  that  tissue  is  usually  ar- 
ranged in  a  special  structure  or  organ,  called  a  gland.  A  brief  state- 
ment of  the  general  characters  and  classification  of  these  organs 
may  here  appropriately  find  a  place. 

Secreting  Glands. — The  simplest  type  of  secreting  structure  con- 
sists of  a  surface  covered  with  a  layer  of  epithelium,  the  cells  of  which 
are  endowed  with  the  power  of  elaborating  a  secretion  and  discharg- 
ing it  upon  their  free  surfaces  (Fig.  32,  6).  The  tissues  supporting 
the  epithelium  belong  to  the  connective  tissues,  and  are  fibrous  in 
character  and  well  provided  with  bloodvessels,  lymphatics,  and 
nerves.  These  bring  to  the  epithelium  the  substances  necessary  for 
its  nourishment  and  work,  and  place  its  activities  under  the  control 
of  the  nervous  system.  Between  the  epithelium  and  the  fibrous 
tissue  supporting  it  there  is  frequently  a  thin  membranous  layer  of 
tissue  that  often  appears  quite  homogeneous,  evidently  belongs  to  the 
connective  tissues,  and  has  received  the  name  of  "basement-mem- 
brane." This  appears  to  offer  a  smooth  surface  for  the  attachment 
of  the  epithelial  cells,  which  receive  their  nourishing  fluids  through  it. 

The  epithelial  surfaces  of  many  of  the  mucous  membranes  are 
examples  of  the  foregoing  simple  secreting  structure.  The  secretory 
function  is  here  of  use  as  an  adjunct  to  the  protective  function 
assigned  to  the  epithelial  covering,  and  the  quantity  of  secretion  is 
but  slight  under  normal  conditions.  Where  the  volume  of  secre- 
tion required  is  considerable  some  provision  for  an  increase  in  the 
extent  of  secreting  surface  is  necessary.  This  may  be  accomplished 
by  an  invagination  of  that  surface,  which  then  forms  the  lining  of 
one  or  more  tubes  or  sacs,  into  which  the  secretion  furnished  by  the 
epithelial  cells  is  discharged.  Such  an  arrangement  of  the  tissues 
constitutes  a  gland,  and  it  is  evident  that  these  may  be  arranged 
into  groups  or  classes  according  to  whether  the  secreting  surface 
forms  a  single  tube  or  sac,  or  several  such  tubes  or  sacs,  uniting  to 
form  a  single  gland.  Thus,  there  may  be  simple  or  compound  tubular 
glands,  or  simple  or  compound  saccular  glands.  Whether  the  deeper 
portions  of  the  gland  have  a  tubular  or  saccular  structure,  the  secre- 


THE  EPITHELIAL   TISSUES. 


59 


tion  of  the  gland  is  discharged  upon  some  free  surface  through  a 
tubular  outlet,  called  the  duct.  This  is  frequently  lined  with  a  non- 
secreting  layer  of  epithelial  cells  differing  in  character  from  the 
actively  secreting  epithelium  in  the  deeper  portions  of  the  glandular 
passages  (Figs.  42-47). 


FIG.  42. 


FIG.  43. 


FIG.  45. 


Diagrams  representing  various  types  of  gland. 

Fig.  42.— Simple  tubular  gland :  a,  epithelium  covering  the  surface  on  which  the  secretion  is 
discharged ;  6,  mouth  of  gland ;  c,  epithelium  lining  the  duct.  This  gradually  passes 
into  the  secreting  epithelium.  Some  simple  tubular  glands  have  no  such  distinction 
between  the  cells  near  the  mouth  and  those  nearer  the  fundus,  but  all  the  cells  are  of  the 
secreting  variety — i.e.,  exercise  that  function,  e,  secretory  epithelium ;  d,  lumen.  The 
sweat-glands  are  simple  tubular  glands  which  are  coiled  in  their  lower  part  to  form  a 
globular  mass. 

Fig.  43.— Compound  tubular  gland  :  /,  duct ;  g,  acinus. 

Fig.  44.— Racemose  tubular  gland  :  /,/,/,  ducts ;  g,  g,  acini. 

Fig.  45.— Simple  saccular  gland :  /,  duct ;  <7,  acinus. 


60 


NORMAL  HISTOLOGY. 
FIG.  46.  FIG.  47. 


Diagrams  representing  various  types  of  gland. 

Fig.  46.— Racemose  saccular  gland:  /,/,  ducts;  g,  acinus. 

Fig.  47.— Compound  tubular  gland,  with  a  marked  distinction  in  the  character  of  the  epi- 
thelium in  the  duct  and  acini :  c,  duct  epithelium  ;  /,  duct ;  d,  lumen  of  the  acinus ; 
e,  secreting  epithelium.  This  type  of  gland  is  common.  This  figure  is  introduced  to  show 
how  difficult  it  might  be  to  detect  the  lumen  of  the  acinus  in  sections  of  such  a  gland. 
The  lumen  is  of  very  small  diameter  (its  size  is  exaggerated  in  this  diagram)  and  runs 
such  a  tortuous  course  among  the  epithelial  cells  that  even  perfect  cross-sections  of  the 
acinus  might  fail  to  reveal  it  if  it  happened  at  that  point  to  run  obliquely  to  the  axis 
of  the  acinus.  It  would  then  appear  merely  as  a  small  clear  spot  upon  the  granular 
cytoplasm  of  the  cell  that  lay  immediately  beneath  it.  s,  s',  represent  the  way  in  which 
two  such  sections  would  contain  portions  of  the  acinus.  The  lumen  in  s'  would  be  more 
easily  detected  than  in  s,  because  its  general  direction  is  more  rectilinear  and  more 
nearly  coincident  with  the  line  of  vision. 

It  is  rarely  possible  to  trace  the  connection  between  the  ducts 
and  other  portions  of  a  gland  in  sections,  for  the  axes  of  these  dif- 
ferent parts  seldom  lie  in  one  plane.  As  a  result  of  this  circum- 
stance, sections  of  glands  usually  present  a  collection  of  round  or 
oval  sections  of  tubes  or  sacs,  which  are  lined  with  a  single  layer  of 
epithelial  cells,  surrounding  a  lumen.  The  cells  in  the  deeper  por- 
tions are  usually  granular  and  cubical ;  those  lining  the  ducts  are 
generally  more  columnar  in  shape  and  less  granular  in  character. 
The  deeper  portions  are  called  the  alveoli  or  acini  of  the  gland,  to  dis- 
tinguish them  from  the  ducts,  and  the  character  of  the  epithelium  they 
contain  differs  according  to  the  function  of  the  gland.  Sometimes 
the  cells  are  so  large  that  they  nearly  fill  the  acini,  leaving  a  scarcely 
perceptible  lumen.  In  other  glands  the  cells  are  less  voluminous 
and  the  lumen  of  each  acinus  is  distinct.  It  occasionally  happens, 
e.g.,  in  the  submaxillary  glands,  that  the  acini  contain  two  sorts  of 
cells  which  secrete  different  materials.  Both  kinds  of  cell  may  be 
present  in  the  same  acinus,  or  each  kind  may  be  confined  to  differ- 
ent acini.  In  studying  sections  of  glands  it  must  be  borne  in  mind 
that  the  tangential  section  of  an  acinus  would  appear  as  a  group  of 


THE  EPITHELIAL   TISSUES. 


61 


cells  surrounded  by  fibrous  tissue,  with  no  trace  of  a  lumen  among 
the  epithelial  cells  (Fig.  48). 

Glands  develop  from  surfaces  which  are  covered  by  epithelium. 

FIG.  48. 


Section  of  gland  from  human  lip.  (Nadler.)  a,  duct,  cut  in  slightly  oblique  direction  (lumen 
oval),  and  probably  near  a  branch,  which  would  account  for  the  apparent  thickness  of 
its  epithelial  lining  in  the  lower  half;  b,  cross-section  of  acinus  secreting  mucus ;  c,  tan- 
gential section  of  a  similar  acinus  near  its  extremity  and  beyond  the  end  of  the  lumen. 
Cross-sections  of  the  cells  at  the  fundus  occupy  the  centre,  d,  cross-section  of  an  acinus 
secreting  a  serous  fluid,  revealing  a  small  lumen ;  d',  a  similar  acinus  with  a  larger  lumen, 
probably  cut  near  its  junction  with  a  duct ;  e,  acinus  with  cresceutic  group  of  cells  with 
granular  cytoplasm  (e'),  and  other  cells  like  those  in  6.  The  granular  cells  of  small  size 
are  considered  to  be  cells  which  have  discharged  their  secretion  and  are  accumulating 
material  for  a  fresh  supply.  /,  nearly  axial  longitudinal  section  of  a  portion  of  a  mucous 
acinus ;  g,  tangential  section  of  a  serous  acinus ;  h,  fibrous  connective  tissue  between  the 
acini ;  i,  capillary  bloodvessel  in  the  fibrous  tissue. 

The  cells  of  this  epithelium  multiply  and  penetrate  into  the  under- 
lying tissues,  forming  little  solid  tongues  or  columns  of  cells  (Fig.  181). 
If  the  gland  is  destined  to  be  of  the  simple  tubular  variety,  this  col- 
umn of  cells  then  becomes  hollowed  to  form  the  lumen,  the  cells  being 


62  NORMAL  HISTOLOGY. 

arranged  in  a  single  layer  lining  the  tubule.  If  the  gland  is  to  be 
compound,  the  solid  column  of  cells  branches  within  the  tissues,  and 
then  the  lumina  of  the  different  portions  are  formed,  the  epithelium 
in  the  different  parts  becoming  differentiated  as  specialization  of 
function  develops. 

The  foregoing  general  description  of  the  structure  of  secreting 
glands  applies  to  those  glands  which  have  a  purely  secretory  func- 
tion, discharging  the  products  of  their  activities  upon  some  free 
surface,  such  as  the  skin  or  a  mucous  membrane.  There  are  other 
glandular  organs  which  perform  more  complicated  functions  and 
the  structure  of  which  deviates  from  that  of  the  simpler  glands. 
Examples  of  these  are  furnished  by  the  liver  and  kidney,  the  struct- 
ures of  which  must  be  deferred  to  a  subsequent  chapter.  Other 
exceptions  are  exemplified  in  the  thyroid  body  and  other  "  duct- 
less "  glands,  which  discharge  no  secretion  into  a  viscus  or  upon  a 
free  surface,  but  which  have  an  alveolar  structure  similar  to  an 
ordinary  secreting  gland.  These  alveoli  do  not  communicate  with 
ducts,  which  are  wanting  ;  but  whatever  products  they  may  con- 
tribute to  the  whole  organism  are  apparently  discharged  into  the 
circulating  fluids  of  the  body  by  a  process  of  absorption  similar  to 
that  through  which  the  glandular  epithelium  obtains  its  materials 
from  those  fluids,  or  by  a  direct  discharge  into  the  lymphatics.  (See 
chapter  on  Ductless  glands.)  This  process  is  indicated  by  the  term 
"  internal  secretion/7  and  is  probably  of  commoner  occurrence  than 
is  usually  supposed.  In  fact,  it  but  represents  a  special  interpretation 
of  the  phenomena  of  interchange  of  material  that  is  constantly  going 
on  between  all  the  cells  of  the  body  and  its  circulating  fluids. 

Epithelium  is  developed  from  the  epiderm  or  hypoderm ;  never 
from  the  mesoderm.  In  this  respect,  as  well  as  in  its  functional 
r6le,  it  differs  from  endothelium. 


CHAPTER   IV. 
THE  CONNECTIVE  TISSUES. 

THE  two  varieties  of  elementary  tissue  that  have  just  been  con- 
sidered— namely,  endothelium  and  epithelium — owe  their  qualities 
directly  to  the  characters  of  the  cells  that  enter  into  their  composi- 
tion. The  intercellular  substances  are  insignificant  in  amount  and 
subordinate  in  function. 

In  marked  contrast  to  these  are  the  tissues  composing  the  group 
known  as  the  "  connective  tissues."  Here  the  usefulness  of  the 
tissues  depends  upon  the  character  of  the  intercellular  substances 
which  confer  upon  the  tissues  their  physical  properties.  The 
activities  of  the  cells  entering  into  the  composition  of  these  tissues 
appear  to  be  confined  to  the  production  of  those  important  inter- 
cellular substances  and  the  maintenance  of  their  integrity.  The 
cells  may,  therefore,  be  considered  as  of  secondary  importance  in 
determining  the  immediate  usefulness  of  the  tissues,  the  first  place 
being  given  to  the  intercellular  substances.  As  was  stated  in  the 
introductory  chapter,  these  connective  tissues  are  essentially  passive 
— i.  <?.,  they  are  useful  because  of  their  physical  characters  rather 
than  because  of  any  ability  to  transform  either  matter  or  energy. 
Where  the  ability  to  accomplish  those  transformations  is  of 
importance  the  tissues  are  found  to  be  essentially  cellular  in  char- 
acter, as  we  have  already  seen  to  be  the  case  in  the  epithelial  tis- 
sues. 

The  connective  tissues  may  be  divided  into  three  main  groups : 
the  cartilages,  bone,  and  the  fibrous  tissues.  Each  of  these  groups 
has  certain  general  structural  characters  that  distinguish  it  from 
the  other  elementary  tissues,  but  within  each  group  there  are 
varieties  which  differ  considerably  in  the  detailed  character  of  their 
intercellular  substances  and  in  the  arrangement  of  these  with  re- 
spect to  the  cells. 

All  the  elementary  tissues  belonging  to  the  connective- tissue 
group  are  developed  from  the  mesoderm. 

63 


64  NORMAL  HISTOLOGY. 

I.  THE  CARTILAGES. 

General  Characters. — (1)  The  typical  cell  of  cartilage  is  round  or 
oval  in  shape,  rich  in  cytoplasm,  and  possesses  one  (rarely  two) 
nucleus  of  oval  form  and  vesicular  and  reticulated  structure. 
Within  the  cytoplasm  there  are  frequently  one  or  more  clear  spots, 
which  are  drops  of  homogeneous  fluid,  "  vacuoles."  The  cells  fre- 
quently depart  somewhat  from  this  type.  Where  the  tissue  is 
growing  they  are  usually  flattened  on  the  sides  turned  toward  their 
nearest  neighbors.  This  is  because  they  are  the  offspring  of  a  cell 
that  has  recently  divided,  and  are  as  yet  separated  by  only  a  small 
amount  of  intercellular  substance.  Under  these  circumstances  each 
cell  is  frequently  surrounded  by  a  thin  layer  of  intercellular  sub- 
stance, probably  of  relatively  recent  formation,  which  differs  a  little 
from  that  further  from  the  cell  and  gives  an  appearance  as  though 
the  cell  were  enclosed  in  a  capsule.  In  older  cartilage  this  appear- 
ance is  no  longer  evident.  Where  cartilage  is  being  replaced  by 

FIG.  49. 


b 

Hyaline  cartilage.  Section  of  human  costal  cartilage :  a,  nearly  spherical  cell  containing 
two  vacuoles ;  6,  recently  formed  intercellular  substance  ("  matrix  "),  separating  two  cells 
that  have  been  produced  by  the  division  of  a  single  cell.  There  are  several  other 
examples  of  a  similar  grouping  of  cells,  due  to  the  same  cause,  in  the  figure.  Between 
the  cells  is  the  hyaline,  nearly  structureless  "matrix." 

bone,  "  ossification,"  the  cells  are  arranged  in  columns,  with  only  a 
small  amount  of  intervening  intercellular  substance,  and  have  a 
general  cubical  form. 


THE  CONNECTIVE  TISSUES. 


65 


(2)  The  intercellular  substance  is  abundant  in  amount  and  has 
received  the  special  designation  "  matrix."     According  to  the  char- 
acter of  this  matrix,  the  cartilages  have   been  divided  into  three 
varieties  :    hyaline   cartilage,   fibro-cartilage,   and  elastic  cartilage. 
In  hyaline  cartilage  the  matrix  is  clear  and  homogeneous  and  has 
the  consistency  of  gristle.     In  fibro-cartilage  it  is  traversed  by  or 
nearly    wholly   composed    of  delicate    fibres    similar   to   those   of 
white  fibrous  tissue,  which  will  be  described  presently.     In  elastic 
cartilage  the  matrix  contains  coarse,  branching,  and  anastomosing 
fibres  similar  to  those  of  elastic  fibrous  tissue  (vide  infra]. 

(3)  The  arrangement  of  the  cells  and   intercellular  substances 
varies   considerably.      Sometimes   the   cells   are    pretty   uniformly 
distributed  throughout  the  intercellular  substance.    Sometimes  they 

FIG.  50. 


Hyaline  cartilage  and  perichondrium.  Human  costal  cartilage.  Same  specimen  as  Fig.  49 . 
a,  group  of  cells  formed  by  division,  but  not  yet  separated  by  matrix ;  &,  matrix ;  c,  cells 
with  a  comparatively  slight  amount  of  cytoplasm,  marking  the  transition  from  cartilage 
to  fibrous  tissue  ;  d,  perichondrium,  composed  of  fibrous  tissue  (spindle-shaped  cells  with 
a  fibrous  intercellular  substance). 

are  arranged  in  groups  of  from  two  to  four  or  even  six  cells.  To- 
\vard  the  surface  of  a  piece  of  cartilage  the  cells  are  apt  to  be  smaller 
than  those  nearer  the  centre,  and  are  frequently  flattened.  Here, 
also,  they  often  lose  the  characters  that  distinguish  them  in  the 
body  of  the  tissue,  and  more  and  more  closely  resemble  the  cells  of 
the  fibrous  tissue  surrounding  the  cartilage.  This  fibrous  tissue 
is  called  the  "  perichondrium,"  and  is  usually  not  sharply  defined 
from  the  cartilage  itself,  the  matrix  of  the  latter  becoming  more 
and  more  fibrous  in  character  and  the  cells  less  distinctly  like  those 

5 


66 


NORMAL  HISTOLOGY. 


FIG.  51. 


Hyaline  cartilage.  Section  from 
human  thyroid  cartilage. 
(Wolters.)  a,  perichondrium ; 
b,  peripheral  zone  of  cartilage 
with  flattened  cells.  In  the 
deeper  portions  of  the  car- 
tilage the  cells  are  larger,  are 
arranged  in  groups,  and  are 
surrounded  by  recently 
formed  matrix.  The  cells  in 
the  deepest  portions  of  the 
cartilage  are  vacuolated,  and 
about  the  groups  of  cells  are 
fine  granules  of  lime  salts. 
In  the  matrix  are  numerous 
anastomosing  lines,  which  are 
interpreted  as  fine  canals,  serv- 
ing to  carry  nourishment  to 
the  cells  in  the  cartilage. 

tion  some  of  the   cells 


typical  of  cartilage  until  the  distinction 
between  the  two  tissues  is  lost.  The  peri- 
chondrium is  wanting  over  the  free  surfaces 
of  the  articular  cartilages. 

1.  Hyaline  Cartilage  (Figs.  49,  50,  and 
51). — Although  under  ordinary  powers  of 
the    microscope   and    in  specimens    which 
have    not    been    specially    prepared    the 
matrix  of  hyaline  cartilage  appears  clear 
and   almost,    if   not    quite,    homogeneous, 
closer  study  reveals  the  presence  of  a  fine 
network  within  the  clear  intercellular  sub- 
stance.    This  network  is  thought  to  be  a 
system  of  minute  channels  through  which 
the    nutrient   fluids    permeate    the   tissue 
and  reach  its  cells.     It  may  be,  however, 
that  this  reticulum  is  of  fibrous  character^ 
in  which   case  the  fibres   might  be  more 
pervious  than  the  surrounding  matrix,  and 
bear  the  same  relations  to  the  nutrition  of 
the  tissue  as  a  system  of  minute  channels. 
In  sections  stained  with  hsematoxylin  the 
matrix  of  hyaline  cartilage  often  acquires  a 
faint  bluish  tinge,  the    cytoplasm   of   the 
cells   a   deeper  shade   of  the    same  color? 
and   the    nuclear   chromatin   a  very  dark 
blue. 

Hyaline  cartilage  forms  the  costal  car- 
tilages, the  thyroid  cartilage,  the  ensiform 
process  of  the  sternum,  the  cartilages  of 
the  trachea  and  bronchi,  and  the  tem- 
porary cartilages  which  are  subsequently 
replaced  by  bone. 

2.  Fibro-cartilage    (Fig.  52).— This    va- 
riety of  cartilage  is  found  in  only  a  few 
situations  :  in  the  interarticular  cartilages 
of  joints,   in    some   of  the  synchondroses, 
in    one    region    in    the    heart,  and    in  the 
intervertebral  disks.     In  the  latter  situa- 

possess  branching  processes,  extending  for 


THE   CONNECTIVE  TISSUES. 


67 


some  distance   between    the    fibres  of  the   intercellular  substance, 
and  giving  the  whole  tissue  a  character  closely  resembling  that  of 


FIG.  52. 


Fibro-cartilage.    Section  from  human  intervertebral  disk.    (Schafer.)    The  cell  to  the  left 
presents  a  branching  process  extending  into  the  intercellular  substance. 

white  fibrous  tissue.       The    cells  are,  however,  more  cytoplasmic 
than  those  of  ordinary  fibrous  tissue. 

3.  Elastic  Cartilage  (Figs.  53  and  58). — This  form  of  cartilage 

FIG.  53. 


Elastic  cartilage.  Section  from  cartilage  of  human  external  ear.  (Bohm  and  Davidoff.) 
a,  cartilage-cell ;  6,  c,  network  of  elastic  fibres  in  the  intercellular  substance;  6,  with  large 
meshes ;  c,  fine-meshed.  Opposite  a  is  a  cell  showing  indications  of  a  division  of  the 
cyptoplasm  following  division  of  the  nucleus. 

is  found  in  the  epiglottis,  the  cornicula  of  the  larynx,  the  ear,  and 
the  Eustachian  tube.  The  coarseness  of  the  anastomosing  fibrous 
network  of  the  matrix  varies  in  different  situations  and  in  different 


68  NORMAL  HISTOLOGY. 

parts  of  the  same  piece  of  cartilage.  The  reticulum  is  usually 
more  open  and  composed  of  larger  fibres  toward  the  centre  of  the 
tissue  than  at  the  periphery,  where  it  becomes  more  delicate  and 
finally  blends  with  the  fibrous  intercellular  substance  of  the  peri- 
chondrium. 

It  is  evident,  both  from  the  structure  of  the  cartilages  and  from 
the  situations  in  which  they  are  found,  that  they  constitute  elastic 
tissues  suitable  for  diminishing  the  effects  of  mechanical  shock. 
This  is  obviously  the  case  in  the  joints,  where  both  the  hyaline 
and  the  fibrous  varieties  are  found.  Their  elasticity  and  moderately 
firm  consistency  are  also  of  obvious  utility  in  the  larynx  and  other 
air-passages  and  in  the  ear,  nose,  and  synchondroses. 

II.  BONE. 

General  Characters. — (1)  The  cells  of  bone,  called  "  bone-corpus- 
cles/' have  an  oval  vesicular  nucleus,  surrounded  by  a  moderate 
amount  of  cytoplasm,  which  is  prolonged  into  delicate  branching 
processes  that  join  those  of  neighboring  cells.  (2)  The  intercellular 
substance  is  composed  of  an  intimate  association  of  an  organic 
substance  and  salts  of  the  earthy  metals.  (3)  The  arrangement 
of  these  constituents  is  as  follows  :  the  organic  basis  of  the  inter- 
cellular substance  is  arranged  in  laminae,  which  are  closelv  applied 
to  each  other  except  at  certain  points  where  there  are  cavities,  called 
"lacunae/'  giving  lodgement  to  the  bone-corpuscles.  Joining  these 
lacunae  with  each  other  are  minute  channels  in  the  intercellular 
substances,  "  canaliculi,"  which  are  occupied  by  the  fine  processes 
of  the  corpuscles.  In  the  compact  portions  of  the  long  bones,  and 
wherever  the  osseous  tissue  is  abundant,  the  laminae  are  arranged 
concentrically  around  nutrient  canals,  the  "  Haversian  canals," 
which  traverse  the  bone,  anastomosing  with  each  other  and  contain- 
ing the  nutrient  bloodvessels  of  the  tissue.  In  cancellated  bone 
these  Haversian  canals  are  absent,  and  the  thin  plates  of  bone  are 
made  up  of  parallel  laminae  of  intercellular  substance,  between 
which  are  the  lacunae,  connected  with  each  other  by  canaliculi.  The 
bone-corpuscles  are  nourished  from  the  fluids  circulating  in  the 
marrow,  which  occupies  the  large  spaces  of  this  spongy  variety  of 
bone. 

It  is  not  possible  in  a  single  preparation  to  study  even  these  gen- 
eral characters  of  bone.  The  earthy  salts  in  the  intercellular  sub- 


THE  CONNECTIVE  TISSUES.  69 

stance  prevent  the  preparation  of  sections  by  means  of  the  knife, 
and,  unless  they  be  removed,  specimens  of  bone  must  be  made  by 
grinding.  This  can  best  be  accomplished  after  the  bone  has  been 
dried.  But  drying  the  bone  destroys  the  corpuscles,  which  appear 
as  little  desiccated  masses,  devoid  of  structure,  within  the  lacunae. - 
Ground  sections  of  bone  can,  therefore,  give  only  an  idea  of  the 
intercellular  substance  and  the  arrangement  of  the  lacunae,  eanal- 
iculi,  Haversian  canals,  etc.  (Fig.  54).  Sections  may  be  cut  if 

FIG.  54. 


Ground  section  of  dried  bone.  Human  femur,  a,  Haversian  canal  in  cross-section ;  a',  Ha- 
versian canal  occupied  by  debris  ;  a",  anastomosing  branch  from  a',  in  nearly  longitud- 
inal section;  b,  lacuna  belonging  to  the  Haversian  system,  of  which  a!  occupies  the 
centre ;  c,  lacuna  in  excentric  laminse  of  bone  between  the  Haversian  systems.  The 
delicate  lines  connecting  the  lacunae  are  the  canaliculi. 

the  bone  be  first  decalcified — i.  e.,  if  the  earthy  salts  be  dissolved 
through  the  action  of  acids.  This  treatment  not  only  removes  the 
earthy  constituents  of  the  intercellular  substance,  rendering  it  soft 
and  pliable,  but  causes  the  organic  constituents  to  swell.  The 
effect  of  this  swelling  upon  the  appearance  of  the  bone  is  very 
marked.  The  fine  canaliculi  are  closed  and  the  lacuna  diminished 
in  size,  so  that  the  structure  of  the  bone  appears  much  simplified, 
being  reduced  to  a  nearly  homogeneous  mass  of  intercellular  sub- 
stance in  which  there  are  spaces  arranged  in  definite  order  and 
enclosing  the  somewhat  compressed  bone-corpuscles.  The  delicate 
processes  of  the  latter  are  not  discernible  within  the  canaliculi,  but 
blend  with  the  swollen  intercellular  substance  forming  the  walls  of 
those  minute  channels.  It  is  important  that  the  student  should 
learn  to  recognize  these  mutilated  preparations  of  bone,  since  it  is 


70  NORMAL  HISTOLOGY. 

in  this  form   that  the  tissue  will  most  frequently  come   under  his 
observation  (Fig.  55). 

Minute  study  of  the  structure  of  the  intercellular  substance  of 
bone  makes  it  appear  that  the  organic  basis  is  not  homogeneous, 
but  is  composed  of  minute  interlacing  fibres,  held  together  by 

FIG.  55. 


Section  of  decalcified  bone,  parallel  to  axis  of  human  femur,  a,  longitudinal  section  of 
Haversian  canal  giving  off  transverse  branch  to  the  left;  b,  tangential  section  of  a  trans- 
verse branch  ;  c,  lacuna  occupied  by  bone-corpuscle ;  d,  intercellular  substance  deprived 
of  its  earthy  salts  and  so  swollen  that  the  canaliculi  are  obliterated. 

a  cement  or  "  ground  "  substance,  containing  the  deposit  of  earthy 
salts.  To  these  salts,  which  are  chiefly  phosphate  and  carbonate 
of  calcium,  the  bone  owes  its  hardness,  while  the  fibres  contribute 
toughness  and  elasticity  to  the  tissue.  The  general  arrangement 
of  the  fibres  in  the  intercellular  substance  is  in  laminae,  which  have 
a  general  parallel  direction  ;  but  there  are  occasional  fibres  of  some 
size  which  pierce  these  laminae  in  a  perpendicular  direction  and 
appear  to  bind  them  together,  very  much  as  a  nail  would  hold 
a  series  of  thin  boards  in  place,  "Sharpey's  fibres." 

Bone  occurs  in  two  forms,  the  compact  and  the  cancellated. 
These  do  not  diifer  in  the  nature  of  the  tissue  itself,  but  merely 
in  the  arrangement  of  that  tissue  with  respect  to  its  sources  of 
nourishment.  Where  the  bone  is  massed  in  compact  form,  as  in 
the  shafts  of  the  long  bones,  special  means  for  supplying  it  with 
nourishment  is  provided  by  a  series  of  channels,  the  Haversian 


THE  CONNECTIVE  TISSUES.  71 

( "in;! Is,  which  contain  the  nutrient  bloodvessels,  and  which  anasto- 
mose with  each  other  throughout  the  whole  substance  of  the  tissue. 
The  nourishing  lymph,  derived  from  the  blood,  reaches  the  cells 
through  the  canaliculi  and  lacunae,  which  connect  with  each  other 
to  form  a  network  of  minute  channels  and  spaces  pervading  the 
bone,  and  not  only  opening  into  the  Haversian  canals,  but  also  upon 
the  external  and  internal  surfaces  of  the  tissue. 

In  the  shafts  of  the  long  bones  the  Haversian  canals  lie  for  the 
most  part  parallel  with  the  axis  of  the  bone,  with  short  transverse 
branches  connecting  them  with  each  other.  It  is  around  these  lon- 
gitudinal Haversian  canals  that  the  laminse  of  bone  are  arranged 
in  concentric  tubular  layers.  Each  Haversian  canal,  with  the 
laminae  surrounding  it,  is  known  as  an  Haversian  system.  Between 
these  Haversian  systems  there  are  excentric  laminae  of  bone,  which 
do  not  conform  to  the  concentric  arrangement  of  the  Haversian 
systems. 

In  the  spongy  or  cancellated  variety  of  bone  the  thin  plates  of 
that  tissue  derive  their  nourishment  from  the  lymph  of  the  con- 
tiguous marrow  filling  the  spaces  between  them,  and  there  is  no 
occasion  for  Haversian  canals.  The  concentric  arrangement  of  the 
laminae  is,  therefore,  absent, 

Except  where  bounded  by  cartilage  at  the  joints,  the  external 
surfaces  of  the  bones  are  covered  by  a  fibrous  investment,  the 
periosteum,  in  which  the  bloodvessels  supplying  the  bone  ramify 
and  subdivide  before  sending  their  small  twigs  into  the  Haversian 
canals  of  the  compact  bone.  The  deep  surface  of  the  periosteum 
contains  connective-tissue  cells,  "  osteoblasts,"  capable  of  assuming 
the  functions  of  bone-corpuscles  and  producing  bone.  These  facts 
explain  the  importance  of  the  periosteum  for  the  nutrition  and 
growth  of  bone.  The  tendons  and  ligaments  attached  to  the 
bones  merge  with  the  periosteum,  which  has  a  similar  fibrous  struct- 
ure and  serves  to  connect  them  firmly  with  the  surface  of  the 
bone. 

The  central  cavities  of  the  long  bones  and  the  spaces  of  cancel- 
lated bone  are  occupied  by  marrow,  which  may  be  of  two  kinds,  the 
"  red  "  or  the  "  yellow."  A  description  of  the  structure  of  marrow 
must  be  deferred  until  the  other  varieties  of  the  connective  tissues 
have  been  considered. 

In  the  embryo  the  parts  which  are  destined  to  become  bony  first 
consist  of  some  other  variety  of  connective  tissue,  either  cartilage 


72  NORMAL  HISTOLOGY. 

or  fibrous  tissue.  This  subsequently  "  ossifies/'  during  which  pro- 
cess it  is  not  really  converted  into  bone,  but  is  gradually  absorbed 
as  that  tissue  develops  and  replaces  it. 


III.  THE  FIBROUS  TISSUES. 

General  Characters. — This  group  of  elementary  tissues,  which 
may  be  said  to  constitute  the  connective  tissues  par  excellence, 
includes  a  number  of  varieties  which  are  not  very  sharply  defined, 
because  of  transitional  modifications  which  bridge  over  the  differ- 
ences between  the  more  distinct  types.  It  will,  therefore,  be  best 
to  describe  these  well-marked  types  of  structure,  and  then  to  indi- 
cate the  direction  in  which  they  are  modified  in  particular  cases  so 
as  to  simulate  in  greater  or  less  degree  other  typical  varieties  of  the 
same  group. 

(1)  The  cells  of  the  fibrous  tissues  vary  considerably  in  character, 
three  more  or  less  distinct  forms  being  distinguishable.  First,  flat- 
tened, almost  membranous  cells  with  oval  nuclei  and  nearly  clear 
and  homogeneous  bodies,  possibly  identical  with  the  cells  that  form 
endothelium  ;  second,  granular  cells,  rich  in  cytoplasm  and  usually 
ovoid  or  cubical  shape,  though  sometimes  elongated ;  third,  elon- 
gated or  fusiform  cells,  with  oval  nuclei  surrounded  by  a  moderate 
amount  of  cytoplasm  which  is  frequently  prolonged  into  processes 
of  greater  or  less  length  and  delicacy,  and  sometimes  dividing  into 
branches.  These  three  sorts  of  cell  are  present  in  varying  relative 
proportions  in  the  different  tissues  belonging  to  this  group.  (2) 
The  intercellular  substance  is  composed  of  distinct  fibres,  asso- 
ciated with  a  homogeneous  cement-  or  "  ground-substance,"  lying 
between  the  fibres.  The  fibres  are  of  two  kinds  :  the  "  white," 
non-elastic,  and  the  elastic  or  "  yellow."  The  relative  abundance 
of  these  and  of  the  ground-substance  associated  with  them,  and 
also  their  arrangement,  vary  greatly  in  the  different  members  of 
the  group.  (3)  The  arrangement  of  the  constituents  of  the  fibrous 
tissues  in  the  different  varieties  is  so  diverse  that  a  statement  of  the 
variations  would  amount  to  a  description  of  the  tissues  themselves. 
The  general  characters  already  enumerated  will  serve  to  distinguish 
the  whole  group  from  all  the  other  elementary  tissues,  and  enable 
the  student  to  recognize  the  fact  that  a  given  form  of  the  tissue 
which  he  may  have  under  observation  belongs  to  this  group. 

Before  entering  upon  a  description  of   the  varieties  of  fibrous 


THE  CONNECTIVE  TISSUES. 


FIG.  56. 


tissue,  it  will  be  of  advantage  to  note  the  peculiarities  of  the  two 
kinds  of  fibres  that  are  found  in  their  inter- 
cellular substance. 

The  white,  non-elastic  fibres  (Fig.  56)  are 
exceedingly  delicate,  and  appear,  even  under 
high  powers  of  the  microscope,  as  fine,  trans- 
parent, homogeneous  lines.  They  are  usu- 
ally aggregated  into  bundles  of  greater  or  less 
thickness,  being  held  together  by  a  small 
amount  of  the  cement-substance  already  re- 
ferred to.  In  these  bundles  the  fibres  run  a 
somewhat  wavy  course  from  one  end  of  the 
bundle  to  the  other,  but  lie  parallel  to  each 
other  and  never  branch.  When  treated  with 
dilute  acetic  acid,  without  previous  hardening, 
they  swell  and  become  almost  invisible.  They 
are  converted  into  gelatin  when  boiled  in  water. 

The  yellow,  or  elastic,  fibres  (Figs.  57-59)  are  coarser  than  the 

FIG.  57. 


Fibres  of  white  fibrous 
tissue  teased  apart  to 
show  the  individual 
fibrils. 


Elastic  fibres. 

Fig.  57.— From  the  subcutaneous  areolar  tissue  of  the  rabbit.    (Schafer.) 
Fig.  58.— Section  of  ear.    (Hertwig.)    The  intercellular  substance  contains  a  reticulum  of 

coarse  anastomosing  elastic  fibres.    (See  Fig.  53.) 
Fig.  59.— Fenestrated  membrane  from  a  branch  of  human  carotid  artery.    (Triepel.) 

white  and  more  highly  refracting,  appearing  more  conspicuous  when 
viewed  under  the  microscope.    They  may  be  nearly  straight,  but  more 


74 


NORMAL  HISTOLOGY. 


usually  run  a  sinuous  course.  At  intervals  they  divide,  and  the 
branches  anastomose  with  each  other  to  form  a  fibrous  network,  the 
meshes  of  which  may  be  large,  as  is  the  case  in  areolar  tissue,  or  so 
small  and  bounded  by  such  broad  fibres  that  the  network  resembles 
a  membrane  pierced  by  somewhat  elongated  apertures,  as  is  exem- 
plified in  the  fenestrated  membranes  of  the  arteries.  The  forma- 
tion of  such  a  network  is,  however,  not  an  essential  characteristic 
of  these  fibres,  for  they  appear  as  isolated  wavy  fibres  in  some  of 
the  fibrous  tissues  of  open  and  loose  structures.  Elastic  fibres  are 
not  affected  by  acetic  acid,  nor  do  they  yield  gelatin  on  boiling  in 
water.  According  to  Schwalbe,  they  have  a  tubular  structure,  con- 
sisting of  a  membrane  enclosing  a  substance  called  "  elastin." 

We  may  now  turn  our  attention  to  the  different  varieties  of  the 
fibrous  tissues. 

FIG.  60. 


Mucous  tissue.  (Ranvier.)  a,  stellate  cells  with  long  and  branching  processes;  6,  elastic  fibres 
in  the  homogeneous,  mucoid,  intercellular  substance,  which  is  not  visible  under  the 
microscope  unless  artificially  colored.  Three  of  the  cells  are  represented  in  cross-section. 


1.  Mucous  Tissue  (Fig.  60). — The  cells  of  this  elementary  tissue 
are  chiefly  of  the  third  variety  mentioned  above.  They  are  spindle- 
shaped  or  stellate  in  form,  and  many  of  them  possess  processes 
that  extend  far  into  the  intercellular  substance,  where  they  may 
branch  and  unite  with  the  processes  of  neighboring  cells.  The 
predominant  constituent  of  the  intercellular  substance  is  a  gelatinous 
ground-substance,  which  contains  a  variable  amount  of  mucin  and 
appears  nearly,  if  not  quite,  homogeneous  under  the  microscope. 
It  is  this  which  gives  the  whole  tissue  its  soft  and  gelatinous  con- 
sistency. A  variable  number  of  fibres  of  both  the  kinds  already 
described  run  through  this  ground-substance.  The  white  fibres  are 


THE  CONNECTIVE  TISSUES. 
FIG.  61. 


fl  «> 


75 


r^f 1  ;u^ 


^  7<^%^x 

--'-^-'         £^s.  --<i^-^  < 


rXY 


F 


Embryonic  connective  tissue  (mesenchymatous  tissue).  (Bohm  and  Davidoff.)  a,  nucleus 
of  stellate  cell ;  6,  cytoplasmic  process.  The  intercellular  substance  is  of  gelatinous  con- 
sistency and  optically  homogeneous. 

arranged  in  fine  bundles,  but  the  elastic  fibres  appear  to  be  isolated, 
and,  though  they  may  branch,  do  not  appear  to  form  a  network. 

FIG.  62. 


Reticular  tissue.  Section  through  a  lymph-sinus  in  a  lymph-node  of  the  rabbit.  (Ribbert.) 
o,  nuclei  of  stellate  cells  of  the  reticulum ;  6,  endothelial  cells  which  are  closely  applied 
to  the  reticulum.  The  lymphoid  cells,  or  leucocytes,  have  been  removed  from  the 
meshes  of  the  reticulum. 

Mucous  tissue  of  a  rather  highly  cellular  character  is  abundant 
in  the  embryo,  where  it  constitutes  an  early  stage  in  the  development 
of  the  fibrous  tissues  (Fig.  61).  A  variety  less  rich  in  cells  forms 


76  NORMAL  HISTOLOGY. 

the  Whartonian  jelly  of  the  umbilical  cord.  It  does  not  occur  in 
the  adult  under  normal  conditions,  except,  perhaps,  in  the  vitreous 
humor  of  the  eye. 

2.  Reticular  Tissue  (Fig.  62). — The  fibres  of  this  variety  of  ele- 
mentary tissue  are  disposed  in  extremely  delicate  bundles,  which 
anastomose  with  each  other  to  form  a  fine  meshwork.     The  spaces 
between  the  fibrous  bundles  are  filled  with  lymph,  which  is  usually 
so  crowded  with  cells  similar  to  the  white  blood-corpuscles  that  the 
structure  of  the  tissue  is  masked  by  their  presence.     The  cells  of 
this  tissue  are  flattened  and  closely  applied  to  the  surfaces  of  the 
bundles  of  fibres,   which  are   so  fine  that  they  simulate   delicate 
branching  processes  emanating  from   the  cells.      The  cement-  or 
ground-substance  is  reduced  to  a  minimum,  only  a  small  amount 
lying  between  the  fibres  and  the  cells  of  the  reticulum.    The  tissue  is 
bounded  by  denser  forms  of  fibrous  tissue,  with  the  fibrous  bundles 
of  which  the  reticulum  is  continuous.     It  is  possible  that  reticular 
tissue  contains  stellate  cells  of  the  third  variety  mentioned  as  occur- 
ring in  fibrous  tissues,  as  well  as  the  thin  cells  already  described, 
which  belong  to  the  first  variety.      Where  this   is  the   case  it  is 
probable  that  the  branching  processes  of  those  cells  take  part  in  the 
formation  of  the  reticulum. 

Where  the  meshes  of  the  reticulum  are  crowded  with  lymphoid 
cells — i.  e.,  cells  identical  with  some  of  the  white  corpuscles  of  the 
blood — the  tissue  has  received  the  name  "  lymphadenoid  tissue." 
This  tissue  is  the  chief  constituent  of  lymph-glands  and  follicles, 
and  is  also  found  in  a  more  diffuse  arrangement  in  many  of  the 
mucous  membranes  (Fig.  107,  L). 

3.  Areolar  Tissue. — This  is  the  most  widely  distributed  variety 
of  fibrous  tissue.     It  contains  all  three  kinds  of  cells  mentioned  at 
the  beginning  of  this  section,  though  not  always  in  the  same  relative 
abundance.     The  intercellular  substance  consists  chiefly  of  bundles 
and  laminse  of  fibres,  which  interlace  in  all  directions.     The  white 
fibres  predominate  over  the  elastic,  but  there  are  always  some  of  the 
latter  which  either  form  a  wide-meshed  reticulum,  interlacing  with 
the  bundles  of  white  fibres,  or  are  applied  to  the  latter  in  a  sort  of 
open  spiral,  binding  them  together.     In  the  developing  tissue  the 
cement-  or  ground-substance  at  first  fills  all  the  interspaces  between 
the  cells  and  the  fibres ;  but  as  development  proceeds  spaces  appear 
in  the  tissue,  which  are  occupied  by  lymph  and  intercommunicate 
throughout  the  tissue.     The  ground-substance  is  then  restricted  to 


THE  CONNECTIVE  TISSUES. 


77 


a  mere  cement  uniting  the  fibres  within  the  bundles  and  lamina. 
The  flat  or  endothelial  cells  of  the  tissue  lie  within  these  bundles  or 
arc  applied  to  their  surfaces,  forming  a  more  or  less  perfect  lining 
to  the  lymph-spaces  within  the  tissue  and  becoming  continuous  with 
the  endothelial  walls  of  the  lymphatic  vessels.  It  is  within  these 
spaces  that  the  lymph  accumulates  after  its  passage  through  the 
walls  of  the  smaller  bloodvessels,  to  find  its  way  into  the  lymphatic 
circulation.  The  spindle-shaped  and  cuboidal  cells  of  the  tissue  lie 
between  or  within  the  bundles  of  fibres  embedded  in  the  cement- 
substance  (Figs.  63  and  64). 

FIG.  63. 


\ 


Areolar  tissue.  Preparation  from  the  subcutaneous  tissue  of  a  young  rabbit.  (Schiifer.) 
c',  endothelioid  cell;  p,p,  cells  with  granular  cytoplasm  ;  c,  c,  f,  cells  of  the  fusiform  or 
stellate  variety  not  yet  fully  developed.  The  white  fibres  are  in  bundles  pursuing  a  wavy 
course  ;  the  elastic  fibres  are  delicate  and  form  a  very  open  network ;  g,  leucocyte  of  a 
coarsely  granular  variety. 

Areolar  tissue  varies  greatly  in  different  situations  in  the  density 
of  its  structure — i.  e.,  in  the  size  of  the  fibrous  bundles  and  their 
relative  abundance,  as  compared  with  the  number  and  size  of  the 
spaces  separating  them.  The  name  is  derived  from  that  form  in 
which  the  structure  is  open  and  the  courses  of  the  fibrous  bundles 
very  diverse,  so  that  they  interlace,  leaving  relatively  large  spaces 
between  them.  In  this  form  it  occurs  in  the  subcutaneous  tissues, 
between  the  muscles,  forming  the  loose  fascia?  in  that  situation,  and 
in  many  other  parts  of  the  body  where  adjacent  structures  are 
looselv  connected  with  each  other.  The  sinuous  course  of  the  in- 


78 


NORMAL  HISTOLOGY. 


FIG.  64. 


-fb 


terwoven  fibrous  bundles  renders  the  tissue  easily  distensible  in  all 
directions  and  permits  considerable  freedom  of  motion  between  the 
parts  which  it  unites. 

In  other  situations  the  spaces  in  the  tissue  are  smaller  and  the 

fibrous  bundles  closer  together 
and  less  tortuous  in  their  arrange- 
ment, so  that  the  parts  connected 
with  each  other  are  more  firmly 
held  in  place.  This  form  of  the 
tissue  occurs  in  all  the  glandular 
organs  of  the  body,  supporting 
and  holding  in  place  the  func- 
tionally active  tissues  of  the  or- 
gans and  constituting  the  chief 
constituents  of  their  interstitia 
(see  Chapter  VII.).  To  distin- 
guish this  form  of  fibrous  tissue 
from  the  areolar  or  more  open 
form  it  may  be  designated  as 
connective  tissue  in  a  more  re- 
stricted use  of  that  term  than 
has  hitherto  been  employed  (Fig. 
65,  b,  &')• 

A  still  denser  form  of  the  tis- 
sue occurs  in  the  fasciae  and  apo- 
neu roses,  in  which  the  fibres  are 
aggregated  in  thick  bundles  and 
layers  that  run  a  comparatively 
straight  course  and  are  firmly  held 
together.  Ligaments  and  tendons  differ  from  these  only  in  the 
greater  density  of  the  fibrous  bundles  and  in  their  parallel  arrange- 
ment. These  denser  varieties  of  the  tissues  may  be  designated  by 
a  restricted  use  of  the  term,  fibrous  tissue. 

4.  Adipose  Tissue  (Fig.  65).— Fat  or  adipose  tissue  is  a  modifica- 
tion of  the  more  open  or  loosely-textured  areolar  tissue,  caused  by 
the  accumulation  within  the  cytoplasm  of  the  cnboidal  cells  of  drops 
of  oil  or  fat,  The  cells  which  have  become  the  seat  of  this  fatty 
infiltration  are  enlarged,  and  their  cytoplasm,  with  the  enclosed 
nucleus,  is  pressed  to  one  side,  the  great  bulk  of  the  cell  being  occu- 
pied by  a  single  large  globule  of  fat.  This  globule,  together  with 


Cell  from  subcutaneous  tissue  of  human 
embryo.  (Spuler.)  c,  centrosome;  fb, 
fibrillse  in  the  cytoplasm  of  the  cell ;  fb', 
fibril  detached  from  the  cell,  but  evi- 
dently derived  from  it.  This  cell  corre- 
sponds to  c,  c,  and/,  in  Fig.  63.  They  are 
sometimes  called  fibroblasts  because  of 
their  activity  in  the  formation  of  fibres. 


THE  CONNECTIVE  TISSUES. 


79 


the  cytoplasm,  is  enclosed  in  a  delicate  cell-membrane.  The  fatty 
cells  may  occur  singly  in  the  midst  of  an  apparently  normal  areolar 
tissue  of  the  usual  type,  but  they  are  more  frequently  grouped  to 
form  "  lobules,"  held  in  position  within  the  tissue  by  bands  and 
layers  of  unaltered  areolar  tissue. 

In  sections  of  adipose  tissue  prepared  after  hardening  the  tissue 
in  alcohol  the  fatty  globules  can  no  longer  be  seen,  since  the  alco- 
hol dissolves  the  fat  from  the  tissues.  The  partially  collapsed 

FIG.  65. 


Section  from  the  tongue  of  a  rabbit :  a,  a,  a,  groups  of  fat-cells  forming  small  masses  of  adipose 
tissue  in  the  connective  tissue ;  6,  b',  connective  tissue,  6  in  longitudinal,  and  6'  in 
cross-section ;  c,  small  vein  containing  a  few  red  blood-corpuscles.  Near  the  centre  of 
the  figure  is  another  bloodvessel  filled  with  corpuscles.  The  remainder  of  the  figure 
represents  striated  muscle-fibres  in  nearly  longitudinal  section.  In  the  upper  left  hand 
corner  these  show  a  tendency  to  split  into  longitudinal  fibres  (sarcostyles). 

membranes  of  the  cells,  with  the  cytoplasm  and  contained  nucleus 
forming  an  apparent  thickening  at  one  side,  are  all  that  remain  to 
distinguish  the  tissue  (Fig.  65,  a). 

Adipose  tissue  is  widely  distributed  in  the  body.  It  serves  as  a 
store  of  fatty  materials  which  can  be  drawn  upon  as  a  reserve 
stock  of  food  when  the  nutrient  supply  of  the  body  falls  below  its 
needs. 

The  usefulness  of  the  fibrous  tissues  can  be  readily  inferred 
from  their  structure.  The  more  open  varieties  of  areolar  tissue 
serve  to  give  support  to  the  structures  they  unite  and  to  the  blood- 
vessels, lymphatics,  and  nerves  supplied  to  them.  They  also  afford 
spaces  and  channels  for  the  return  of  the  lymph,  which  transudes 
through  the  walls  of  the  capillary  bloodvessels,  carries  nourishment 


80  NORMAL   HISTOLOGY. 

to  the  tissue-elements  it  bathes,  and  then  returns  to  the  blood  in 
the  veins  through  the  interstices  and  lymphatic  vessels  contained  in 
the  areolar  tissue.  In  pursuance  of  these  functions,  areolar  tissue 
pervades  nearly  all  parts  of  the  body.  Wherever  bloodvessels 
are  found,  there  more  or  less  areolar  tissue  is  present,  surrounding 
them,  giving  them  support,  and  furnishing  channels  for  the  lym- 
phatic circulation.  As  has  already  been  stated,  this  areolar  tissue 
varies  in  the  closeness  of  its  texture  in  different  parts  of  the  body. 
The  fibrous  tissues  of  tendons  and  ligaments  form  inextensible 

FIG.  66. 


c 

Portion  of  a  large  tendon  in  transverse  section.  (Schafer.)  a,  sheath  of  areolar  tissue  sur- 
rounding the  tendon ;  6,  longitudinal  fasciculus  of  fibres  within  that  sheath  ;  I,  lymphatic 
space;  c,  section  of  a  broad  extension  of  the  ensheathing  areolar  tissue,  dividing  the 
tendon  into  larger  bundles ;  d,  e,  more  delicate  layers  of  areolar  tissue  subdividing  the 
larger  bundles  of  fibres.  Between  these  areolar  septa  are  the  bundles  of  fibres  constitut- 
ing the  tendon.  The  cells  which  lie  between  the  smallest  fasciculi  of  fibres  appear  in 
stellate  form:  the  cross-sections  of  the  individual  fibres,  among  which  these  cells  lie, 
are  not  represented.  They  would  appear  as  minute  dots. 

bands  or  cords  highly  resistant  to  tensile  stress,  but  very  pliable. 
They  consist  of  bundles  of  fibres  lying  parallel  to  each  other  .and  to 
the  direction  in  which  they  are  to  resist  pulling  forces.  Layers  of 
loose  areolar  tissue  penetrate  the  ligaments  and  tendons,  dividing 
them  into  fasciculi,  which  in  turn  are  united  into  larger  bundles  by 
thicker  layers  of  areolar  tissue  (Fig.  66).  These  sheaths  of  areolar 
tissue  support  the  vessels  and  nerves  supplied  to  the  denser  forms 
of  the  fibrous  tissue  making  up  the  ligaments  or  tendons.  The 
thicker  aponeuroses  of  the  body  may  be  regarded  as  broad  and  flat 


THE  CONNECTIVE  TISSUES.  81 

ligaments,  in  which  the  bundles  of  fibres  run  in  various  directions. 
They  present  a  structural  transition  between  the  fibrous  arrange- 
ment in  ligaments  and  tendons  and  that  in  the  more  open  varieties 
of  areolar  tissue.  The  fibres  of  these  tissues  are  mostly  of  the 
white  variety,  but  in  some  situations,  notably  in  the  ligamentum 
nuchse,  they  are  chiefly  of  the  elastic  variety. 

Reticular  tissue  may  be  regarded  as  a  special  modification  of 
areolar  tissue,  in  which  the  main  bulk  of  the  tissue  consists  of  a 
series  of  freely  intercommunicating  lymph-spaces.  These  are  often 
densely  crowded  with  lymphoid  cells,  among  which  the  lymph 
slowly  circulates,  thereby  being  subjected  to  the  modifying  influ- 
ences of  their  activities. 


CHAPTER  Y. 
TISSUES  OF  SPECIAL  FUNCTION. 

THE  elementary  tissues  included  in  this  group  are  highly  differ- 
entiated in  structure  so  as  to  adapt  them  for  the  performance  of 
some  special  function  of  a  high  order.  The  constituent  of  the 
tissues  which  appears  most  highly  specialized  is  the  cell,  which  is 
often  so  greatly  modified  in  structure  as  to  have  lost  many  of  the 
general  characters  of  the  cells  hitherto  studied.  Thus,  for  example, 
the  cells  of  striated  muscle  are  multinucleated,  and  the  cytoplasm 
has  become  transformed  into  a  substance  known  as  contractile  sub- 
stance, which  occupies  nearly  the  whole  bulk  of  the  cell,  leaving 
only  a  small  amount  of  relatively  undifferentiated  cytoplasm  imme- 
diately surrounding  the  nuclei. 

In  like  manner  the  intercellular  substances  of  some  of  these 
tissues  show  a  complexity  of  structure  in  great  contrast  to  those 
with  which  we  have  become  familiar  in  the  preceding  tissues.  In 
fact,  it  is  stretching  a  point  to  regard  the  tissues  lying  between  the 
cells  of  striated  muscle  as  forming  an  intercellular  substance 
belonging  to  that  tissue.  In  this  case  those  tissues  are  identical 
in  structure  with  the  loose  areolar  tissue  that  was  described  in  the 
preceding  chapter.  We  may,  therefore,  with  propriety,  regard  the 
striated  muscles  as  organs  in  which  the  muscle-cells  constitute  the 
parenchyma  and  this  areolar  tissue  the  interstitium  (see  Chapter 
VII.).  But  in  other  tissues  of  the  group  there  is  either  an  inter- 
cellular substance  resembling  those  of  the  preceding  tissues,  or 
some  special  form  of  sustentacular  tissue — e.  g.,  the  neuroglia  of 
the  central  nervous  system. 

The  tissues  of  special  function  are  arranged  in  two  groups  :  the 
muscular  tissues  and  the  nervous  tissues.  As  is  implied  in  the 
title,  these  tissues  are  grouped  together  because  of  their  functional 
powers,  and  not  with  regard  to  peculiarities  of  structure,  so  that  it 
is  impossible  to  give  concise  statements  of  any  common  general 
structural  characters  possessed  by  all  the  members  of  each  of  these 

82 


TISSUES  OF  SPECIAL  FUNCTION.  83 

two  groups.  Thus,  the  individual  muscular  tissues  differ  consider- 
ably from  each  other  in  structure,  but  are  closely  related  in  function, 
each  variety  being  specialized  so  as  to  execute  a  particular  kind  of 
contraction  when  functionally  active.  We  must  also  assume  that 
the  variations  in  structure  met  with  in  the  nervous  system  have 
reference  to  the  translation  of  various  impressions  into  nervous 
impulses,  or  the  liberation  of  such  impulses  under  different  condi- 
tions, as  well  as  to  their  transmission  and  application  to  the  func- 
tional activities  of  other  tissues. 

The  complex  functions  exercised  by  the  nervous  system  appear 
to  necessitate  a  great  variety  of  nervous  structures,  and  it  would 
be  a  matter  for  surprise  to  find  the  visible  structure  of  the  nervous 
system  as  simple  as  it  is,  were  it  not  for  the  fact,  already  learned, 
that  cells  apparently  similar  in  structure  may  have  widely  different, 
though  related,  functional  powers. 

I.  THE  MUSCULAR  TISSUES. 

There  are  three  varieties  of  muscular  tissue,  which  differ  from 
each  other  both  in  structure  and  in  the  character  of  their  functional 
activities.  One  variety  is  that  found  in  the  walls  of  the  hollow 
viscera  and  larger  bloodvessels.  Its  activities  are  not  under  the 
control  of  the  will,  and  the  cells  are  devoid  of  marked  cross-stri- 
ation  of  the  contractile  substance.  It  has,  therefore,  received  the 
names,  "  involuntary  "  or  "  smooth  "  muscular  tissue.  The  other  two 
varieties  present  distinct  and  rather  coarse  cross-stria tion  of  the 
contractile  substance,  but  differ  in  other  structural  details.  One  of 
these  is  called  "voluntary"  or  "  striated  "  muscle;  the  other  is  found 
only  in  the  heart,  is  not  under  the  control  of  the  will  except  in 
rare  instances,  and  is  known  as  "cardiac"  muscular  tissue. 

1.  Smooth  Muscular  Tissue. — This  elementary  tissue  is  composed 
of  elongated  or  fusiform  cells,  which  gradually  taper  to  a  sharp 
point.  The  body  of  the  cell,  except  close  to  the  ends  of  the  nucleus, 
consists  of  a  modified  cytoplasm,  called  "contractile  substance," 
which  stains  a  coppery  red  with  eosin,  and  presents  fine,  indistinct, 
longitudinal  and  transverse  markings,  possibly  the  optical  expression 
of  certain  ridges  that  are  in 'contact  with  similar  ridges  on  neigh- 
boring cells.  Each  cell  has  a  single,  greatly  elongated,  rod-shaped 
nucleus  situated  in  its  centre,  with  the  long  axis  coincident  with 
that  of  the  cell  (Fig.  67).  The  nuclei  are  vesicular  and  possess 


84 


NORMAL  HISTOLOGY. 


FIG.  67. 


a  distinct  intranuclear  reticulum  of  chromatin.  The  intercellular 
substance  is  a  mere  cement  of  homogeneous  character. 
rpjie  cej]s  are  arrailge(j  with  their  long  axes  parallel  to 
each  other  and  with  the  tops  of  their  minute  ridges  in 
contact,  so  that  fine  channels  exist  between  the  contiguous 
cells.  This  is  apparently  a  provision  for  the  circulation 
of  nutrient  fluids  between  the  cells  (Fig.  68). 

Smooth  muscular  tissue  occurs  in  the  form  of  bundles 
or  layers,  in  each  of  which  the  cells  or  fibres  run  in  the 
same  direction.  The  tapering  ends  of  the  individual  cells 
interdigitate  with  each  other,  masking  the  intercellular 
substance,  so  that  the  tissue  appears  as  though  wholly 
composed  of  cells.  Surrounding  the  muscular  bundles  or 
between  the  layers  of  that  tissue  is  vascularized  areolar 
tissue,  giving  it  support  and  containing  its  nerve-supply. 

The  microscopical  appearances  of  sections  of  smooth 
muscular  tissue  depend  upon  the  direction  in  which  the 
individual  cells  have  been  cut.  A  brief  analysis  of  the 
different  appearances  that  may  result  will  be  useful  as  an 

FIG.  68. 


Smooth  muscular  tissue. 

Fig.  67.— An  isolated  fibre  from  the  muscular  coat  of  the  small  intestine.  (Schafer.)  The 
nucleus  is  somewhat  contracted,  so  as  to  appear  broader  and  shorter  than  when  in  the 
extended  state. 

Fig.  68.— Cross-section  of  smooth  muscular  tissue :  human  sigmoid  flexure.  (Barfurth.)  Two 
of  the  muscle-cells  have  been  cut  in  the  region  occupied  by  the  nucleus,  which  appears 
in  round  cross-section.  The  other  cells  have  been  cut  between  the  site  of  the  nucleus 
and  the  end  of  the  cell.  The  structural  details  of  the  cytoplasm  or  contractile  substance 
are  not  represented,  but  the  connecting  ridges  of  the  cells,  with  the  channels  between 
them,  are  shown.  These  minute  ridges  can,  however,  only  be  seen  when  the  tissue  has 
been  exceptionally  well  preserved  and  is  studied  under  a  high  power  of  the  microscope. 

illustration  of  the  way  in  which  microscopical  appearances  must  be 
interpreted  in  order  to  gain  a  correct  conception  of  the  structure 


TISSUES  OF  SPECIAL  FUNCTION.  85 

of  an  object  under  observation.  It  is  rarely  that  sections  happen 
to  be  made  in  such  a  direction  that  they  reveal  the  complete  struct- 
ure of  an  object.  It  is  nearly  always  necessary  to  study  the  appear- 
ances presented  by  the  section,  and  to  infer  what  the  structure  of 
the  object  must  be  in  order  to  yield  the  appearances  seen.  This  is 
sometimes  a  matter  of  considerable  difficulty. 

If  the  plane  of  the  section  lie  parallel  with  the  long  axes  of 
the  cells,  the  nuclei  of  the  latter  will  appear  as  rod-like  or  long, 
oval  bodies  lying  parallel  to  each  other  and  distributed  at  regular 
intervals  throughout  the  tissue.  The  outlines  of  the  cells  will  be 
distinctly  visible  in  some  places,  but  in  most  of  the  section  the 
boundaries  of  the  deeper  cells  will  be  obscured  by  the  bodies  of 
the  cells  at  the  surface  of  the  section,  and  the  borders  of  the  latter 
will  be  difficult  of  detection,  because  in  many  places  the  knife  has 
left  only  a  portion  of  the  cell  with  a  very  thin  and  transparent 
edge  (Figs.  69  and  70).  For  the  practical  recognition  of  the  tissue, 
when  cut  in  this  direction,  we  must,  therefore,  in  many  cases, 
depend  solely  upon  the  shape  and  distribution  of  the  nuclei  and 
the  color  of  the  material  between  them  after  the  section  has  been 
treated  with  certain  stains  (e.  g.,  eosin). 

If  the  cells  of  the  tissue  have  been  cut  perpendicular  to  their 
loner  axes,  the  section  will  contain  true  cross-sections  of  the  indi- 

o 

vidual  fibres.  These  appear  as  round,  oval,  or,  more  usually, 
polygonal  areas  of  various  size,  according  to  the  part  of  the  cell 
included  in  the  section.  If  the  cell  has  been  cut  near  one  of  its 
ends,  the  cross-section  will  be  small  ;  if  near  the  middle,  it  will  be 
large,  and  will  contain  a  cross-section  of  the  nucleus,  situated  near 
its  centre  and  appearing  as  a  round  dot  (Fig.  71).  It  is  in 
such  sections  that  one  may  sometimes  see  the  minute  prickles 
or  ridges,  already  referred  to,  projecting  from  the  cell-bodies 
and  joining  with  those  of  the  contiguous  cells  to  form  delicate 
bridges  across  the  narrow  intercellular  spaces.  The  only  tissue 
with  which  this  aspect  of  smooth  muscular  tissue  is  liable  to  be 
confounded  is  dense  fibrous  tissue,  as  seen  in  the  cross-sections  of 
tendons  or  ligaments  (Fig.  66).  There  we  also  see  polygonal  areas 
of  various  sizes,  separated  for  the  most  part  by  only  a  thin  layer  of 
cement.  But  these  areas  never  contain  nuclei,  because  they  are 
composed,  not  of  cell-bodies,  but  of  intercellular  substance.  The 
nuclei  of  the  flattened  connective-tissue  cells  may  be  seen  here  and 
there  apparently  lying  within  the  cement,  the  body  of  the  cell  being 


86 


NORMAL  HISTOLOGY. 


FIG.  69. 


Diagrams  illustrating  the  appearance  of  a  longitudinal  section  of  smooth  muscular  tissue. 

The  distance  between  the  lines  A  A  and  B  B  in  the  upper  figure  represents  the  thickness  of 
the  section,  the  line  A  A  being  in  the  plane  of  its  upper  surface.  The  line  C  C  in  the  lower 
figure  is  in  the  plane  of  the  transverse  section  represented  in  the  upper  figure. 

It  will  be  noticed  that  only  portions  of  the  cells,  h,  a,  d,  c.  and  /,  will  be  contained  in  the 
longitudinal  section  (lower  figure).  The  upper  cut  surfaces  of  those  cells  will  appear  as 
oval  areas  when  seen  from  above,  h',  a',  d',  c',f.  Where  the  edges  of  those  sections  are 
thin — e.g.,  a — the  outlines  of  the  corresponding  oval  (a')  will  be  difficult  of  detection. 
At  the  same  time  those  portions  of  cells  which  lie  at  the  top  of  the  section  will  obscure 
the  outlines  of  the  cells  beneath.  Thus,  at  the  point  6  the  outlines  of  the  cells  i  and  e 
will  be  difficult  of  detection  because  covered  by  the  cells  k  and  a,  and  also  because  the 
cell  i  overlaps  the  cell  e.  If  the  plane  of  junction  were  perpendicular  to  the  surface  of 
the  section,  the  outlines  of  i  and  e  would  be  much  more  clearly  defined. 

This  brief  analysis  will  serve  to  show  that  the  outlines  of  the  cells  will  rarely  be  seen  with 
distinctness  in  longitudinal  sections  of  smooth  muscular  tissue.  On  the  other  hand,  the 
nuclei  of  the  cells  will  be  prominently  visible  in  stained  sections  because  of  the  color 
they  have  received.  For  the  recognition  of  this  tissue,  when  so  cut,  we  must,  therefore, 
depend  chiefly  upon  the  character  and  distribution  of  the  nuclei. 

In  order  to  avoid  an  unnecessarily  complicated  diagram,  many  of  the  cells  represented  in 
the  upper  cut  have  been  omitted  from  the  lower  figure. 


TISSUES  OF  SPECIAL  FUNCTION. 


87 


so  thin  as  often  to  escape  observation.  These  differences  render  it 
easy  to  distinguish  the  two  kinds  of  tissue  in  spite  of  their  general 
similarity  when  seen  in  cross-section. 

It  is,  of  course,  rarely  that  sections  contain  smooth  muscular 


FIG.  71. 


FIG.  72. 


a      bed 


if      ii 
a'    b'    c'   d 


Diagrams  of  smooth  muscular  fibres  cut  in  various  directions. 

Fig.  71.— Fibres  cut  exactly  perpendicular  to  their  long  axes.  The  lines  A  A  and  B  B  in  the 
upper  figure  indicate  the  portions  of  the  fibres  included  in  the  section,  which  is  viewed 
from  above  in  the  lower  figure.  The  cross-sections  of  the  fibres  a  and  &  contain  cross- 
sections  of  the  nuclei ;  those  of  c  and  d  are  smaller  and  devoid  of  nuclei. 

Fig.  72.— Fibres  cut  obliquely  to  their  long  axes.  When  the  upper  surface  of  the  section, 
marked  by  the  line  A  A  in  the  upper  figure,  is  in  sharp  focus,  the  sections  of  fibres  appear 
as  in  a,  b,  c,  and  d  of  the  lower  figure.  When  the  bottom  of  the  section,  indicated  by  the 
line  B  B  in  the  upper  diagram,  is  in  clear  view,  the  sections  of  the  fibres  appear  as  shown 
at  a',  V,  c',  and  d'.  It  will  be  noticed  that  the  optical  section  of  fibre  a  in  the  upper  dia- 
gram has  moved  from  a  to  a'  in  the  lower  diagram.  As  the  focus  was  changed,  the  nucleus 
in  fibre  a  was  constantly  present  and  its  optical  section  appeared  of  uniform  size.  This 
could  only  be  the  case  when  the  nucleus  was  rod-shaped  and  of  the  same  diameter 
throughout  that  portion  contained  in  the  section.  In  the  fibre  d  the  nucleus  was  visible 
when  the  upper  surface  of  the  section  was  in  focus,  but  disappeared  when  the  focal  plane 
was  depressed. 


88 


NORMAL  HISTOLOGY. 
FIG.  73. 


Diagrams  of  smooth  muscular  fibres  cut  very  obliquely.  The  explanation  of  Fig.  72,  already 
given,  will  make  this  one  clear.  In  this  case  the  outlines  of  the  fibres  in  section  will  be 
less  sharply  defined  than  in  the  preceding  case,  because,  for  instance,  at  the  point  a  the 
fibre  a'  is  cut  so  as  to  leave  only  a  thin  edge,  difficult  of  detection,  and  the  fibre  b  has  had 
such  a  thin  slice  removed  from  it  that  the  loss  would  be  hardly  perceptible.  The  appear- 
ance of  the  section  would,  therefore,  be  much  less  easy  of  interpretation  than  is  repre- 
sented in  the  lower  figure,  where  the  outlines  of  the  sections  are  equally  distinct 
throughout. 

tissue  cut  exactly  in  either  of  the  directions  just  considered.  In  the 
majority  of  sections  that  come  under  observation  the  muscle-fibres 
are  cut  obliquely,  and  the  oval  or  polygonal  areas  which  result  are, 
therefore,  elongated.  The  nuclei  of  the  cells  lie  at  an  angle  with 
the  line  of  vision,  and,  in  consequence,  appear  foreshortened.  If 
now  we  focus  the  instrument  so  as  to  get  a  sharp  image  of  the  upper 
surface  of  the  section,  and  then  rapidly  turn  the  fine  adjustment  so 
as  to  bring  the  lower  surface  into  focus,  we  shall  notice  an  apparent 
lateral  motion  of  the  nuclei  and  cell-sections.  This  apparent  lateral 
movement,  due  to  change  of  focus,  is  an  evidence  of  the  elongated 
shape  and  oblique  position  of  the  objects  exhibiting  it ;  and  a  little 
reflection  will  convince  the  student  that  such  oblique  sections,  when 
carefully  studied,  are  better  calculated  to  reveal  the  shapes  and  rela- 
tive positions  of  the  tissue-elements  than  either  perfect  longitudinal 
or  cross-sections.  He  should  seek  to  train  his  powers  of  observa- 
tion so  that  he  may  readily  interpret  the  instructive,  though  at  first 
confusing,  images  presented  by  such  sections  (Figs.  72  and  73). 

Smooth  muscular  tissue  is  not  under  the  direct  control  of  the  will. 
For  this  reason  it  is  frequently  called  "  involuntary  muscle."  It  is 
also  sometimes  designated  as  non-striated  or  unstriped  muscle,  in 
contradistinction  to  the  other  two  varieties  of  muscular  tissue,  the 
fibres  of  which  present  distinct  cross-striations. 

The  functional  contractions  of  smooth  muscular  fibres  are  slug- 
gish. The  fibres  are  slow  in  responding  to  stimulation,  contract 
leisurely,  maintain  the  contracted  condition  for  a  long  time,  and 
then  gradually  relax.  These  properties  render  the  tissue  of  value 


TISSUES  OF  SPECIAL  FUNCTION. 


89 


in  conferring  "tone"  to  certain  structures  in  which  it  is  found, 
notably  the  walls  of  the  arteries  and  veins.  They  also  render  it 
of  service  in  producing  the  vermicular  movements  that  are  essential 
for  the  functional  activity  of  such  organs  as  the  stomach  and  intes- 
tine. 

Smooth  muscular  tissue  has  a  wide  distribution  in  the  body.     It 
is  found  in  greatest  bulk  in  the  uterus,  middle  coats  of  the  arteries 

FIG.  74. 


Diagrams  of  cardiac  muscular  tissue. 

A,  longitudinal  section:  a,  nucleus  of  muscle-cell ;  6,  unmodified  cytoplasm;  c,  contractile 

substance  with  longitudinal  and  transverse  striations ;  d,  cement-substance  uniting  con- 
tiguous cells  ;  e,  areolar  tissue  (vessels  omitted)  between  the  muscle-fibres  formed  by  the 
union  of  the  individual  cells  ;  /,  small  bloodvessel  within  the  areolar  tissue.  If  the  lines 
of  junction  between  the  cells  were  not  visible,  the  tissue  would  appear  as  though  com- 
posed of  interlacing  and  anastomosing  fibres,  none  of  which  could  be  traced  for  any  con- 
siderable distance.  Such  is  the  usual  appearance  of  longitudinal  sections  of  cardiac 
muscle. 

B.  transverse  section :  a,  section  of  a  cell,  including  the  nucleus ;  c,  section  above  the  nucleus 

and  just  below  a  crotch  formed  by  the  divergence  of  a  branch;  6,  section  above  the 
nucleus  and  the  point  where  the  branch  V  is  given  off. 

and  veins,  the  muscular  coats  of  the  stomach  and  intestine,  and  the 
wall  of  the  bladder  ;  but  we  shall  find  it  present  in  greater  or  less 
amount  in  many  of  the  organs,  the  structure  of  which  we  shall 
presently  have  to  study. 

2.  Cardiac  Muscular  Tissue  (Figs.  74  and  75). — The  heart-muscle 
is  composed  of  cells  having  a  general  cylindrical  form  and  contain- 
ing a  single  (occasionally,  two)  nucleus.  The  nucleus  is  vesicular, 
has  a  distinct  reticulum  of  chromatin,  and  is  usually  oval.  It  is 
situated  near  the  centre  of  the  cell,  and  is  surrounded  by  a  small 
amount  of  cytoplasm,  which  is  a  little  more  abundant  at  the  ends 


90 


NORMAL  HISTOLOGY. 


of  the  nucleus.  The  rest  of  the  cell-body  is  composed  of  contractile 
substance,  a  modification  of  the  cytoplasm  of  which  the  cell  was 
first  composed,  which  presents  a  fine  longitudinal  and  a  somewhat 
coarser  transverse  striation.  The  proper  intercellular  substance  is 
a  homogeneous  cement,  which  lies  between  the  ends  of  the  cells. 
These  are  arranged  end  to  end  so  as  to  form  fibres,  the  lines  of 

FIG.  75. 


Section  of  human  heart.  The  direction  of  the  section  is  such  that  the  muscular  cells  are  cut 
exactly  perpendicular  to  their  long  axes,  a,  intermuscular  areolar  tissue.  From  this,  more 
delicate  fibrous  tissue  penetrates  between  the  muscle-fibres  forming  the  muscular  bundles, 
which  are  imperfectly  separated  from  each  other  by  the  broader  septa  of  fibrous  tissue. 
b,  muscle-cell  cut  beyond  the  nucleus  ;  c,  cell  cut  so  as  to  include  the  nucleus ;  d,  cell  cut 
just  below  a  branch.  The  index  line  d  points  to  that  part  of  the  cell  which  passes  into 
the  branch.  The  granular  character  of  the  contractile  substance  when  seen  in  cross- 
section  has  been  omitted  from  the  figure.  At  the  lower  edge  of  the  figure  the  section 
has  been  torn,  but  a  small  amount  of  the  subpericardial  areolar  tissue  is  represented. 

junction  between  the  cells,  which  are  occupied  by  the  cement-sub- 
stance, being  usually  invisible.  The  cells  give  off  branches  which 
unite  with  each  other  in  such  a  way  as  to  convert  the  heart-muscle 
into  a  reticulum  of  muscular  fibres.  The  meshes  of  this  reticulum 
are  occupied  by  areolar  tissue,  in  which  the  vascular  and  nervous 
supply  of  the  tissue  is  situated.  Where  this  tissue  is  abundant  it 
may  also  contain  a  few  fat-cells.  The  cardiac  muscle-cells  are 
destitute  of  a  cell-membrane,  in  which  respect  they  differ  from  the 
voluntary  striated  muscle-fibres. 


TISSUES  OF  SPECIAL  FUNCTION. 


91 


When  seen  in  longitudinal  section  it  is  difficult  to  trace  a  given 
muscle-fibre  for  any  considerable  distance,  because  the  occasional 
anastomosing  branches  of  the  cells  cause  a  blending  of  the  neigh- 
boring fibres  with  each  other.  In  cross-section  the  cells  have  a 
round,  oval,  or  polygonal  shape,  and  vary  considerably  in  size, 
owing  to  the  branching.  Their  cut  surfaces  are  dotted  with  the 
minute  polygonal  cross-sections  of  the  elements  of  the  contractile 
substance,  which  give  the  cell  its  appearance  of  longitudinal  stri- 
ation.  These  elements  are  called  the  "  sarcostyles." 

Cardiac  muscle  occurs  only  in  the  heart.  It  is  not  under  the 
control  of  the  will,  but  differs  from  the  other  involuntary  muscles 
in  the  force  and  rapidity  of  its  contractions,  which  resemble  those 
of  the  voluntary  muscles. 

3.  Striated  Muscular  Tissue  (Figs.  76-79). — The  voluntary  muscles 
have  for  their  characteristic  tissue-element  greatly  elongated,  multi- 


FIG.  76. 


FIG.  77. 


Striated  muscular  tissue. 

Fig.  76.— Portion  of  a  muscle-fibre  from  a  mammal.  (Schafer.)  This  figure  represents  the 
appearances  of  the  fibre  when  the  surface  is  in  sharp  focus. 

Fig.  77.— Termination  of  a  muscle-fibre  in  tendon.  (Ranvier.)  c,  contractile  substance  ;  p, 
retracted  end  of  contractile  substance,  separated  from  the  sarcolemma  during  the  prep- 
aration of  the  specimen ;  m,  sarcolemma,  slightly  wrinkled ;  s,  sarcolemma  in  contact 
with  fibrous  tissue  of  tendon ;  t,  tendon. 


92 


NORMAL  HISTOLOGY. 
FIG.  78. 


FIG.  79. 


Striated  muscular  tissue. 

Fig.  78.— Diagrams  of  the  structure  of  the  contractile  substance.  (Rollet.)  Q,  sarcous  elements, 
appearing  dark  in  A,  light  in  B;  Zand  J,  sarcoplasm.  The  sarcoplasm  also  lies  between 
the  sarcous  elements  in  Q,  appearing  as  light  bands  in  A  and  as  dark  lines  in  B.  A  is  the 
appearance  of  the  fibre  when  the  focal  plane  is  deep ;  B,  the  appearance  when  the  focal 
plane  is  superficial  (see  Fig.  76).  The  dots  Z  in  A  and  J  in  B  are  optical  expressions  of 
differences  in  the  refraction  of  the  sarcoplasm  and  sarcous  elements,  and  do  not  repre- 
sent actual  structures.  A  complete  explanation  of  the  way  in  which  a  microscopical  im- 
age may  contain  apparent  objects  which  have  no  actual  existence  cannot  be  entered  into 
here.  It  is  due  to  the  fact  that  regularly  alternating  structures  of  different  powers  of  re- 
fraction affect  rays  of  light  very  much  as  they  are  affected  by  a  fine  grating,  producing 
diffraction  spectra.  These  spectra  may  interfere  with  each  other,  occasioning  an  alter- 
nation of  light  and  dark  bands  or  areas  above  the  specimen.  When  the  focal  plane  is 
changed  the  light  areas  become  dark  and  the  dark  areas  light,  but  sometimes  with  an 
alteration  in  their  outline  and  relative  sizes,  as  exemplified  in  the  cuts. 

Fig.  79.— Cross-section  of  a  muscle-fibre.  (Rollet.)  The  fine  reticulum,  collected  into  larger 
masses  at  a  few  points  in  the  midst  of  the  contractile  substance,  is  composed  of  sarco- 
plasm. The  clear  areas  within  this  reticulum  are  the  cross-sections  of  the  sarcous  ele- 
ments. These  cross-sections  are  sometimes  called  "Cohnheim's  areas."  Immediately 
beneath  the  sarcolemma  are  cross-sections  of  two  nuclei. 

nucleated,  cylindrical  cells.      The  body  of  these  cells  is  almost  ex- 
clusively composed  of  a  very  complex,  contractile  substance  which  pre- 


TISSUES  OF  SPECIAL  FUNCTION.  93 

sents  both  longitudinal  and  transverse  striations,  the  latter  much  coarser 
and  prominent  than  the  former.  It  must  suffice  us  to  consider  this  con- 
tractile substance  as  made  up  of  a  number  of  prismatic  bodies, 
"  sarcous  elements/7  which  are  arranged  end  to  end  to  form  col- 
umns, sarcostyles,  extending  parallel  to  each  other,  from  one  end 
of  the  cell  to  the  other.  The  sarcous  elements  of  all  the  sarcostyles 
lie  in  planes  perpendicular  to  the  long  axis  of  the  cell.  It  is, 
therefore,  possible  to  separate  the  contractile  substance  into  a 
number  of  fibre-like  columns  (sarcostyles,  Fig.  65),  made  up  of  sar- 
cous elements  attached  at  their  ends,  or  to  split  it  transversely  into 
disks  composed  of  sarcous  elements  lying  side  by  side.  Between 
the  sarcous  elements  is  a  substance  which  has  received  the  name 
"  sarcoplasm." 

The  contractile  substance  is  enclosed  in  a  thin,  homogeneous  mem- 
branous envelope,  called  the  "  sarcolemma."  The  nuclei  of  the  cell  lie 
immediately  beneath  the  sarcolemma,  between  it  and  the  contractile 
substance,  and  are  surrounded  by  a  small  amount  of  unmodified 
cytoplasm. 

The  muscle-fibres  lie  parallel  to  each  other  and  to  the  general 
direction  of  the  muscle  which  they  compose,  and  are  separated  by 
loose  areolar  tissue,  containing  their  vascular  and  nervous  supplies. 
When  seen  in  cross-section  they  are  circular  or  polygonal  in  form, 
and  the  cut  surface  of  the  contractile  substance  appears  crowded 
with  small  polygonal  areas,  the  sections  of  the  sarcous  elements, 
between  which  is  the  sarcoplasm.  Where  the  nuclei  are  included 
in  the  section  they  appear  somewhat  flattened  and  lie  at  the  edge 
of  the  contractile  substance,  where  a  thin  zone  of  cytoplasm  may 
sometimes  be  detected  around  them.  The  sarcolemma  which  lies 
outside  of  these  constituents  of  the  cell  is  so  thin  that  it  can  rarely 
be  distinctly  seen. 

The  muscle-fibres  are  in  close  contact  at  both  ends  with  the  dense 
fibrous  tissue  of  the  tendons  attached  to  the  muscle. 


CHAPTER  VI. 

TISSUES  OF  SPECIAL  FUNCTION  (CONTINUED). 
II.  THE  NERVOUS  TISSUES. 

THE  nervous  tissues,  like  the  muscles,  are  tissues  of  special  func- 
tion, and  are  composed  of  highly  specialized  structures.  Of  these, 
only  the  ganglion-cells,  the  nerve-fibres,  the  neuroglia,  and  a  few  of 

FIG.  80. 


:\    / 


Nerve-  and  neuroglia-cells  from  gray  matter  of  spinal  cord ;  calf.  (Lavdowsky.)  The  figure 
represents  two  isolated  ganglion-cells,  with  branching  protoplasmic  processes,  and  each 
with  a  single  axis-cylinder  process,  en.  The  axis-cylinder  process  of  the  lower  cell  gives 
off  a  branch  a  short  distance  from  the  cell.  Between  the  ganglion-cells  are  those  of  the 
neuroglia.  The  protoplasmic  processes  of  the  nerve-cells  subdivide  into  very  delicate 
fibres,  which  lie  among  those  of  the  neuroglia-cells. 

the  modes  of  terminal  distribution  of  the  nerves  will  be  considered 
here. 

94 


TISSUES  OF  SPECIAL  FUNCTION.  95 

1.  Ganglion-  or  Nerve-cells  (Figs.  80  and  81). — Nerve-cells  vary 
greatly  both  in  shape  and  size.  They  are  rich  in  cytoplasm,  and  con- 
tain an  unusually  large  nucleus,  generally  spherical  in  shape,  within 
the  reticulum  of  which  there  is  nearly  always  at  least  one  conspicu- 

FIG.  81. 


Section  of  unipolar  nerve-cell  from  gray  matter  of  spinal  cord.  (Flemming.)  This  figure 
shows  the  fibrillation  of  the  axis-cylinder  process  and  the  cytoplasm  of  the  cell,  as  well 
as  the  prominent  chromophilic  granules  in  the  latter. 

ous  nucleolus.  The  cell-bodies  may  be  spherical,  ovoid,  polyhedral, 
or  stellate  in  form,  and  are  prolonged  into  one  or  more  long  pro- 
cesses. Some  of  these  taper  and  branch  repeatedly,  the  ultimate 
delicate  fibrils  terminating  in  free  extremities  lying  in  the  inter- 
cellular substance,  "dendritic  processes."  At  least  one  of  the 
processes  emanating  from  each  cell  is  coarser  than  these  dendritic 
processes,  and  is  prolonged  into  a  nerve-fibre,  forming  the  essen- 
tial constituent  of  that  structure.  This  process  is  called  the 
"  axis-cylinder  process."  It  does  not  branch  as  freely  as  the 
other  processes,  but  may  give  off  one  or  more  lateral  twigs  near 
its  origin. 

It  is  customary  to  divide  the  nerve-cells  into  unipolar,  bipolar, 
and  multipolar  cells,  according  to  the  number  of  processes  proceed- 
ing from  them.  The  unipolar  cells  are  connected  by  their  single 
processes  with  nerve-fibres,  and  many  of  the  bipolar  cells,  which 
have  a  fusiform  shape,  lie  in  the  course  of  a  fibre  with  which 
the  two  processes  are  continuous.  In  such  cases  one  of  the 


96  NORMAL  HISTOLOGY. 

processes  is  an  axis-cylinder  process.  The  multipolar  cells  have 
one  axis-cylinder  process,  the  rest  being  of  the  dendritic  type 
already  mentioned,  which  are  distinguished  as  u  protoplasmic " 
processes. 

Nerve-cells  are,  as  a  rule,  larger  than  the  other  cytoplasmic  cells 
of  the  body,  with  the  exception  of  the  larger  epithelial  cells.  Their 
cytoplasm  is  so  finely  granular  that  the  cells  look  much  more  trans- 
parent than  those  of  epithelium.  With  a  high  power  the  cytoplasm 
frequently  exhibits  fine  striations,  which  are  prolonged  into  the 
processes,  giving  them  an  appearance  of  longitudinal  fibrillation. 
These  appearances  are  due  to  the  arrangement  of  the  fibrils  of 
spongioplasm.  Considerable  attention  has  of  late  been  given  to 
certain  granules,  which  become  evident  in  the  cytoplasm  ivhen 
nerve-cells  have  been  fixed  in  alcohol  or  in  acid  solutions.  These 
granules  have  an  affinity  for  dyes,  "  chromophilic  granules,"  and 
usually  occur  in  groups  in  the  neighborhood  of  the  nucleus.  Their 
significance  is  not  yet  understood. 

The  protoplasmic  processes  of  the  nerve-cells  diminish  in  diam- 
eter as  they  branch,  and  they  also  present  occasional  varicosities, 
which  give  them  an  irregular  contour.  They  terminate  either  in 
fine -pointed  extremities  or  in  little,  knobbed  ends,  and  do  not  unite 
with  those  of  neighboring  cells,  but  form  with  them  an  intricate 
interlacement  of  delicate  nervous  twigs. 

The  axis-cylinder  processes  arise  in  conical  extensions  of  the  cell, 
and  then  become  uniform  in  diameter  and  of  a  smooth  contour 
without  varicosities.  When  they  branch  the  two  divisions  retain 
their  size  throughout  their  course  until  they  enter  into  the  forma- 
tion of  some  terminal  structure. 

The  average  size  of  the  nuclei  of  nerve-cells  is  greater  than  that 
of  the  other  nuclei  in  the  body,  but  they  appear  to  contain  less 
chromatin,  and  therefore  stain  less  deeply  and  present  a  less  distinct 
intranuclear  reticulum. 

Nerve-  or  ganglion-cells  are  found  in  the  gray  matter  of  the 
central  nervous  system,  in  the  ganglia,  and  sometimes  in  the  course 
of  nerves  and  in  their  peripheral  terminations  (Fig.  82). 

2.  Nerve-fibres. — There  are  two  varieties  of  nerve-fibres  :  the 
white,  or  medullated,  and  the  gray,  or  non-medullated.  These 
differ  both  in  their  appearance  when  seen  by  the  unaided  eye  and 
in  their  microscopical  structure. 

(a)  Medullated  nerve-fibres  consist  of  a  central  cylindrical  struct- 


TISSUES  OF  SPECIAL  FUNCTION.  97 

ure  running  a  continuous  course  from  the  cell  giving  it  origin  to 
the  peripheral  termination  of  the  nerve,  called  the  "axis-cylin- 
der "  ;  an  external  membranous  envelope,  the  "  neurilemma  "  ;  and 
a  semisolid  material,  the  "myelin,"  "white  substance  of  Schwann," 
or  "  medullary  sheath,"  lying  within  the  neurilemma  and  surround- 
ing the  axis-cylinder. 

The  axis-cylinder   is  a  greatly  elongated  process  (axis-cylinder 
process)  springing  from  a  nerve-cell.     It  is  marked  by  longitudinal 


FIG.  82. 


Small  ganglion  in  the  tongue  of  a  rabbit:  a,  a',  ganglion- cells  ;  a',  cell,  with  the  beginning 
of  its  axis-cylinder  process ;  6,  medullated  nerve-fibre  in  cross-section ;  c,  fibrous  tissue 
within  the  ganglion  (part  of  this  fibrous  structure  may  be  composed  of  non-medullated 
nerve-fibres) ;  d,  areolar  tissue  surrounding  the  ganglion  and  containing  adipose  tissue  in 
the  upper  and  lower  parts  of  the  figure.  To  the  left  is  a  striated  muscle-fibre.  The  gan- 
glion is  seen  in  cross-section,  so  that  its  connection  with  the  nerves,  in  the  course  of  which 
it  lies,  is  not  visible. 


striations,  which  appear  to  represent  exceedingly  delicate  fibrils 
composing  the  axis-cylinder.  These  fibrils  frequently  separate  at 
the  distal  extremity  of  the  nerve  and  take  part  in  the  construction 
of  the  various  forms  of  nerve-endings.  A  more  minute  study  of 
the  axis-cylinder  leads  to  the  inference  that  it  is  composed  of 
spongioplasm,  continuous  with  that  of  the  body  of  the  cell,  and 
that  the  appearance  of  longitudinal  striation  is  due  to  the  elongated 
shape  of  the  spongioplasmic  mesh  work  and  the  greater  thickness 
of  its  longitudinal  threads,  the  transverse  threads  uniting  them 
being  much  less  conspicuous. 


98 


NORMAL  HISTOLOGY. 


FIG.  83.  The  neurilemma,  or  external  in- 

vestment of  the  nerve-fibre,  called 
also  the  (t  primitive  sheath/7  or 
"  sheath  of  Schwann,"  is  a  thin, 
homogeneous  membrane  enclosing 
the  medullary  substance  or  myelin. 
At  regular  intervals,  upon  the  in- 
ner surface  of  the  neurilemma,  and 
surrounded  by  a  small  amount  of 
cytoplasm,  are  flattened,  oval  nu- 
clei, which  appear  to  belong  to  the 
neurilemma.  About  midway  be- 
tween these  nuclei  the  nerve-fibre 
Meduiiated  nerve-fibre.  (Key  jg  COnstricted,  forming  the  "  nodes  " 

andRetzius.)    A,  node  of  Ran- 
vier; B,  nucleus  belonging  to  of  Ranvier.      The  neurilemma  ap- 

*&  1Uft  pears  to  pass  through  these  nodes 
distinct  by  the  retraction  of  without  interruption,  so  that  the 

the  myelin  of  the  medullary  .,  „  .  ,        . 

sheath,  in  the  left-hand  fig-  neurilemma   of    one   internode    is 

ure  the  clefts  of  Lantermann    continuoilS    With    that   of  the    adja- 

are  shown  as  white  lines  in  the 

dark  myelin.  These  figures  are   cent    intemodes.         At    the     nodes, 

ttSSfiS&SE  and    apparently  within  the  neuri- 
the  fatty  constituent  of  the  lemma,  is  a  disk,  perforated  for  the 

myelin  a  dark  brown  or  black.  . 

passage  ot  the  axis-cylinder,  called 

the  "  constricting  band  "  of  Ranvier.  It  may  be  that  this 
band  is  of  the  nature  of  a  cement-substance,  joining  the 
neurilemma  of  neighboring  internodes ;  for  the  latter  ap- 
pear to  be  developed  from  cells,  probably  of  mesoblastic 
origin,  which  surround  the  nerve-fibres  after  their  for- 
mation, becoming  flattened  to  form  membranous  invest- 
ments of  the  nerve-fibre.  If.  this  view  be  correct,  the 
neurilemma  of  each  internode,  with  its  single  nucleus,  is 
to  be  regarded  as  a  single,  specialized  cell,  derived  from 
the  surrounding  connective  tissues,  and  serving  to  protect 
the  nerve-fibre.  In  perfect  harmony  with  this  conception 
of  its  nature  are  the  facts  that  the  nerves  within  the  brain 
and  spinal  cord  are  destitute  of  neurilemma,  and  that  when 
a  nerve-fibre  branches  in  its  course  the  point  of  division 
is  always  at  one  of  the  nodes  of  Ranvier  (Fig.  83). 

The  medullary  sheath,  or  myelin,  is  a  soft  material  inter- 


TISSUES  OF  SPECIAL  FUNCTION. 


99 


posed  between  the  neurilemma  and  axis-cylinder.  It  is  not  a 
simple  substance,  but  contains  at  least  one  constituent  closely  re- 
sembling fat  or  oil  in  its  chemical  nature ;  also  a  substance  chemi- 
cally allied  to  the  keratin  of  horns  and  the  superficial  cells  of  the 
epidermis,  called  neurokeratin ;  and  a  homogeneous,  clear  fluid. 
The  way  in  which  these  constituents  are  combined  is  a  matter  of 
doubt,  the  apparent  structure  of  the  medullary  sheath  varying 
greatly  when  different  modes  of  preparing  the  nerve  for  micro- 
scopical study  have  been  employed.  But  the  neurokeratin  appears 
to  exist  as  a  delicate  reticulum  pervading  the  medullary  substance. 
The  medullary  sheath  appears  to  be  interrupted  at  irregular  inter- 
vals by  oblique  clefts,  which  surround  the  axis-cylinder  like  the 
flaring  portion  of  a  funnel.  These  "  Lantermann's "  clefts  are 
occupied  by  a  soft  material,  probably  similar  to  that  composing  the 
constricting  bands  (Figs.  84  and  85). 


FIG.  84. 


FIG.  85. 


v 


Ax.C. 

Fig.  84.  —  Longitudinal  view  of  portion  of  nerve-fibre  from  sciatic  of  dog.    (Schiefferdecker.) 

S,  neiirilemma  ;  T,  stained  substance'within  the  clefts  of  Lantermann. 
Fig.  85.—  Cross-section  from  sciatic  nerve  of  frog.    (Bohm  and  Davidoff.)    A,  axis-cylinder, 

showing  punctate  sections  of  the  fibrillse  ;  B,  medullary  sheath  stained  with  osmic  acid  ; 

a,  b,  apparent  duplication  of  the  medullary  sheath,  due  to  the  presence  of  a  Lantermann 

cleft  ;  C,  afeolar  tissue  between  the  fibres. 

The  medullary  sheath  is  developed  after  the  formation  of  the 
axis-cylinder,  and  is,  at  first,  continuous  along  the  course  of  the 
latter.  Subsequently  it  becomes  interrupted  at  the  nodes  of 
Ranvier  by  the  constricting  disk.  It  seems  to  be  derived  from 


100 


NORMAL  HISTOLOGY. 


the  axis-cylinder,  and  may,  therefore,  be  regarded  as  a  product  of 
that  greatly  extended  arm  of  the  cytoplasm  of  the  nerve-cell. 

The  amount  of  medullary  substance  present  in  different  nerves 
varies  greatly.  Sometimes  it  is  so  slight  as  to  be  hardly  distin- 
guishable. In  other  cases  its  thickness  considerably  exceeds  the 
diameter  of  the  axis-cylinder.  It  is  present  within  the  spinal  cord 
and  brain,  although  not  enclosed  in  neurilemma  in  those  situations. 

At  the  peripheral  ends  of  the  nerves,  on 
the  contrary,  it  usually  disappears  before 
the  neurilemma. 

The  individual  nerve-fibres  are  isolated 
only  at  their  extremities.  Throughout 
most  of  their  course  they  are  collected 
into  bundles,  forming  the  "  nerves  "  of 
the  body.  Within  these  bundles  the  nerve- 
fibres  are  held  together  by  fibrous  tissue 
in  the  following  manner  :  a  delicate  areolar 
tissue  containing  their  vascular  supply  lies 
between  the  individual  fibres.  This  fibrous 
tissue  is  called  the  "  endoneiirium."  The 
nerve-fibres,  thus  held  together,  are  aggre- 
gated into  bundles,  called  "funiculi,"  which 
are  surrounded  by  sheaths  of  still  denser 
fibrous  tissue,  rich  in  lymphatic  spaces, 
which  are  called  the  "  perineurium."  This 
perineurium  on  its  inner  surface  becomes 
continuous  with  the  endoneurium  just  de- 
scribed. The  funiculi,  enclosed  by  their 
perineurium,  are,  in  turn,  held  together 
by  an  areolar  sheath,  which  has  received 
the  name,  "  epineurium,"  and  forms  the 
outer  covering  of  the  nerve. 

The  funiculi  do  not  run  a  distinct  course 


Nerve-fibres  from  the  sympa- 

'SThe 
that  marked  m  are  non-med- 

ullated.    The  fibre  m  has  an  .•>  •>  .->       -i          ,1         n    ,1  i 

incomplete  medullary  sheath,  throughout  the  length  of  the  nerve,  but 

n,  n,  nuclei  of  the  neurilemma.  cnVQ    off  nerve-bundles,   enclosed    in    peH- 
These  are   surrounded   by  a  .  ,  .   ,      .    .  />      •      T         i 

small  amount  of  cytoplasm,  neurmm,  which  join   other  funiculi  ;   the 

which  is  not  clearly  repre-  nerve-fibres  themselves  do  not,  however, 
anastomose  with  each  other. 


sented  in  the  figure. 


(6)  The  gray,  or  non-medullated,  nerve-fibres  are,  as  their  name 
implies,  destitute  of  medullary  substance.     They  consist  of  an  axis- 


TISSUES  OF  SPECIAL  FUNCTION. 


101 


cylinder,  which  at  intervals  appears  to  be  nucleated.  These  nu- 
clei are  presumably  constituents  of  a  membranous  investment  or 
neurilemma ;  but  the  latter  is  difficult  of  demonstration  because  of 
its  thinness  and  transparency,  and  its  constant  presence  is  not  defi- 
nitely established  (Fig.  86). 

Unlike  the  medullated  variety,  the  gray  nerve-fibres  frequently  give 
off  branches,  which  join  other  fibres  and  constitute  true  anastomoses. 

Non-medullated  fibres  are  most  abundant  in  the  sympathetic 
nervous  system,  but  occur  also  in  the  nerves  derived  directly  from 
the  brain  and  spinal  cord. 

3.  Neuroglia. — The  nerve-cells  and  fibres  of  the  central  nervous 
system  are  surrounded  and  supported  by  a  tissue  which  is  derived 
from  the  epiderm,  and  is  called  the  "  neuroglia."  It  must  be  re- 
garded as  a  variety  of  elementary  tissue  having  functions  similar  to 
the  connective  tissues,  although  its  origin  makes  its  relations  to  the 
epithelial  tissues  very  close. 

Neuroglia  consists  of  cells,  the  "  glia-cells,"  which  vary  consider- 


FIG.  87. 


FIG.  88. 


Glia-cells  from  the  neuroglia  of  the  human  spinal  cord.    (Retzius.) 
Fig.  87.— Three  cells  from  the  anterior  portion  of  the  white  matter:  a,  processes  extending  to 

the  surface  of  the  cord ;  b,  cell-body ;  c,  long,  delicate  process  extending  far  into  the  white 

matter. 
Fig.  88.— Two  cells  from  the  deep  portion  of  the  white  matter. 

ably  in  character,  and  an  intercellular  substance,  which  is  for  the 
most  part  soft  and  homogeneous,  resembling  in  this  respect  the 
cement-substance  found  in  epithelium,  but  which  may,  here  and 
there,  contain  a  few  delicate  fibres,  possibly  derived  from  the  pro- 
cesses of  some  of  the  cells,  or  possibly  of  mesodermic  origin,  and, 
in  consequence,  belonging  to  the  connective  tissues. 


102 


NORMAL  HISTOLOGY. 


The  glia-cells  possess  delicate  processes,  which  lie  in  the  cement- 
or  ground-substance  and  form  a  felt-like  mass  of  interlacing  fila- 
ments, but  do  not  unite  with  each  other.  Two  types  of  cell  may  be 
distinguished,  but  they  are  not  sharply  defined,  because  intermediate 
forms  are  met  with.  In  the  first  type  the  cells  have  relatively  large 

FIG.  89. 
f 


FIG.  90. 


Glia-cells  from  the  human  spinal  cord.    (Retzius.) 
Fig.  89.— Cells  from  the  substantia  gelatinosa  Rolandi  of  the  posterior  horn.    The  cell  to  the 

right  has  a  long  process  beset  with  fine,  bluish  branches. 
Fig.  90.— Four  cells  from  the  gray  matter. 
Figs.  87-90  are  taken  from  specimens  stained  by  Golgi's  method,  which  fails  to  reveal  the 

internal  structure  of  the  cells,  but  is  extremely  well  adapted  to  show  the  shapes  of  the 

cells  and  their  extension  into  fine  processes. 

bodies,  beset  with  a  multitude  of  comparatively  short,  very  fine,  and 
frequently  branching  processes  (Figs.  89  and  90).  This  type  is  most 
frequently  met  with  in  the  gray  matter.  The  second  type  of  glia- 
cell  is  represented  by  cells  with  smaller  bodies  and  longer  and  some- 
what coarser  processes  that  branch  much  less  freely  (Figs.  87  and  88). 
They  also  often  possess  one  particularly  large  and  prominent  proc- 
ess of  greater  length  than  the  others.  The  small  bodies  of  these 
cells  serve  to  distinguish  them  from  nerve-cells,  with  which  they 
might  otherwise  be  easily  confounded.  This  type  predominates  in 
the  white  matter. 

Aside  from  the  processes  of  the  glia-cells  already  mentioned,  the 


TISSUES  OF  SPECIAL  FUNCTION. 


103 


FIG.  91. 


central  nervous  system  contains  fibrous  prolongations  of  the  epi- 
thelial cells  of  the  ependyma  and  central  canal  of 
the  spinal  cord  (Fig.  91).  Fibrous  constituents  are 
also  derived  from  the  areolar  tissue  which  extends 
into  the  organs  of  the  central  nervous  system  from 
their  fibrous  investments,  the  pia  mater,  in  company 
with  the  vascular  supply. 

The  central  nervous  system,  then,  consists  of  a 
small  amount  of  a  ground-substance  and  a  great 
number  of  cells,  most  of  which  possess  numerous 
delicate  fibrillar  processes  which  interlace  in  all 
directions.  Some  of  these  cells  are  the  function- 
ally active  elements  of  the  organs,  the  nerve-cells. 
Others  belong  to  the  sustentacular  tissue,  and  are 
probably  functionally  passive,  constituting  the  in- 
ters titium.  Both  kinds  of  cell  are  developed  from 
the  epiderm,  and  are  therefore  genetically  closely 
related  to  each  other. 

4.  Nerve-endings. — Nerve-fibres  terminate  in  two 
ways  :  first,  in  free  ends  lying  among  the  elements 
of  the  tissues  to  which  the  nerve  is  distributed ; 
second,  in  terminal  organs,  containing  not  only 
nerve-filaments,  but  cells  which  are  associated  with 
them  to  form  a  special  structure.  The  simplest 
mode  of  termination  consists  in  a  separation  of  the  minute  fibrillse 

FIG.  92. 


Ependyma  and  glia- 
cells  from  the  spi- 
nal cord.  (Retzius.) 
a,  ependyma  in  the 
wall  of  the  central 
canal ;  b,  neuroglia- 
cell  near  the  ante- 
rior fissure  of  the 
cord. 


Termination  of  nerves  by  free  ends.  (Retzius.)  Nerve-endings  among  the  ciliated  columnar 
epithelium  on  the  frog's  tongue.  Two  goblet-cells,  the  whole  bodies  of  which  are  colored 
black,  are  represented.  The  other  cells  are  merely  indicated. 

composing  the  axis-cylinders  of  the  medullated  fibres,  or  the  chief 
bulk  of  the  non-medullated  fibres,  into  a  number  of  delicate  fila- 


104 


NORMAL  HISTOLOGY. 
Fro.  93. 


Fi«.  94. 


Termination  of  nerves  by  free  ends.    (Retzius.) 
Fig.  93.— Two  nerves  terminating  in  the  stratified  epithelium  covering  the  vocal  cords  of  the 

cat. 

Fig.  94.— Nerve-fibres  distributed  among  the  cells  lining  the  bladder  of  the  rabbit :  o,  super- 
ficial layer  of  the  transitional  epithelium ;  bg,  fibrous  tissue  underlying  the  epithelium. 

ments,  which  branch  and  finally  end  among  the  tissue-elements  to 
which  the  nerve  is  supplied.  The  filaments  often  present  small  vari- 
cosities,  and  sometimes  end  in  slight  enlargements  corresponding  to 
one  of  those  swellings.  In  other  cases  the  terminations  are  filiform 
(Figs.  92-94). 

A  more  complex  mode  of  termination  is  that  exemplified  in  the 
"  motor-plates  "  of  the  striated  muscle-fibre.    Here  the  axis-cylinder 


TISSUES  OF  SPECIAL  FUNCTION.  105 

divides  into  coarse  extensions,  which  form  a  network  of  broad  vari- 
cose fibres,  lying  in  a  finely  granular  material  containing  two  sorts 
of  nuclei.  This  whole  structure  lies  in  close  relations  to  the  con- 
tractile substance  of  the  muscle-fibre,  but  whether  it  is  covered  by 
the  sarcolemma  or  not  is  a  matter  of  doubt.  The  nuclei  in  the 
motor-plate  are  derived  in  part  from  the  muscle-fibre,  from  the 
cytoplasm  of  which  the  granular  material  surrounding  the  nerve- 

FIG.  95. 


b 

Motor-plate.  Tail  of  a  squirrel.  (Galeotti  and  Levi.)  a,  two  branches  of  axis-cylinder  ter- 
minating in  a  plexus  of  varicose  filaments ;  6,  muscle-nucleus ;  c,  nucleus  derived  from 
neurilemma.  The  finely  granular  substance  surrounding  these  structures  has  been 
omitted. 

endings  appears  to  be  derived,  in  part  from  cells  similar  to  those 
forming  the  neurilemma,  which  participate  in  the  production  of  the 
motor-plate  (Fig.  95). 

The  nerves  of  sensation,  like  those  supplying  the  striated  muscles, 
end  in  bodies  in  which  the  nervous  terminations  are  associated  with 
cellular  structures  of  peculiar  form.  Their  consideration  will  be 
postponed  until  the  structure  of  the  nervous  system  is  described. 


CHAPTER   VII. 
THE  ORGANS. 

IN  the  lowest  order  of  animals,  the  protozoa,  the  single  cell, 
which  constitutes  the  whole  individual,  performs  all  the  functions 
necessary  to  the  life  of  the  animal ;  but  in  the  higher  multicellular 
animals,  the  raetazoa,  those  functions  are  distributed  among  a  num- 
ber of  different  but  definite  structures,  called  organs,  each  of  which 
is  composed  of  certain  of  the  elementary  tissues  arranged  according 
to  a  definite  and  characteristic  plan  peculiar  to  the  organ. 

Within  each  organ  certain  of  the  elementary  tissues  are  charged 
with  the  immediate  performance  of  the  function  assigned  to  that 
organ.  These  tissues  are  collectively  termed  the  parenchyma  of 
the  organ.  Thus,  for  example,  the  epithelium  entering  into  the 
composition  of  the  liver  and  doing  the  work  peculiar  to  that  organ, 
constitutes  its  parenchyma.  The  parenchyma  of  the  heart  is  its 
muscular  tissue,  through  the  activity  of  which  it  is  enabled  to  con- 
tract upon  its  contents. 

Functionally  ancillary  to  its  parenchyma,  each  organ  possesses  a 
variety  of  elementary  tissues,  some  of  which  belong  to  the  connec- 
tive-tissue group,  which  serve  to  hold  the  tissue-elements  of  the 
parenchyma  in  position,  to  bring  to  them  the  nutrient  fluids  neces- 
sary for  their  work,  and  to  convey  to  them  the  nervous  stimuli 
which  excite  and  control  their  functional  activities.  These  sub- 
sidiary tissues  are  collectively  known  as  the  interstitium  of  the 
organ.  For  example,  the  fibrous  tissue  and  the  elementary  tissues 
forming  the  bloodvessels,  lymphatics,  and  nerves  of  the  liver,  or  of 
the  heart,  form  the  interstitia  of  those  organs. 

Two  sets  of  structures  entering  into  the  formation  of  the  inter- 
stitia of  the  organs — namely,  the  nerves  and  the  vessels,  including 
those  which  convey  blood  and  those  through  which  the  lymph  cir- 
culates— have  a  similar  general  structure  in  all  the  organs,  and  are 
connected  with  each  other  throughout  the  body,  forming  "  systems." 
These  systems  serve  to  bring  the  various  parts  of  the  body,  so 
diverse  in  structure  and  function  and  yet  so  interdependent  upon 

106 


THE  ORGANS.  107 

each  other,  into  that  intimate  correlation  that  makes  them  subordi- 
nate parts  of  a  single  organism. 

Through  the  medium  of  the  circulatory  system  the  exchanges  of 
material  essential  to  the  well-being  of  each  organ  and  of  the  whole 
body  are  made  possible,  and  through  the  nervous  system  the  activ- 
ities of  the  different  parts  of  the  body  are  so  regulated  that  they 
work  in  harmony  with  each  other  and  respond  to  their  collective 
needs. 

Because  of  their  wide  distribution  throughout  the  body,  we  can 
hardly  study  any  structures  which  are  not  in  intimate  relations  with 
both  vessels  and  nerves.  It  will,  therefore,  be  well  to  consider  the 
structure  of  the  circulatory  system  before  proceeding  to  a  study  of 
other  organs.  The  study  of  the  nervous  system  must,  because  of 
its  complexity,  be  deferred. 


CHAPTER  VIII. 
THE  CIRCULATORY  SYSTEM. 

THE  circulatory  system  is  made  up  of  organs  which  serve  to  pro- 
pel and  convey  to  the  various  parts  of  the  body  the  fluids  through 
the  medium  of  which  those  parts  make  the  exchanges  of  material 
incident  to  their  nutrition  and  functional  activities. 

For  some  of  these  exchanges  it  appears  necessary  for  the  circu- 
lating fluids  to  come  into  the  most  intimate  contact  with  the  tissue- 
elements  ;  to  penetrate  the  interstices  of  the  tissues  and  bathe  their 
structures.  For  mechanical  reasons  these  fluids  must  circulate 
slowly  and  consume  a  considerable  time  in  traversing  a  relatively 
short  distance.  Such  a  sluggish  current  could  not  avail  for  the 
transportation  of  oxygen  from  the  lungs  to  the  tissues,  and  we 
find  that  the  circulatory  system  is  divided  into  two  closely  related 
portions :  the  haematic  circulation  and  the  lymphatic  circulation. 
The  former  is  rapid,  and  the  circulating  fluid  is  the  blood,  the  red 
corpuscles  of  which  serve  as  carriers  of  oxygen.  The  latter  is  slow, 
and  the  circulating  fluid,  called  "  lymph,"  is  derived  from  the  liquid 
portion  of  the  blood  ("  the  plasma  ").  The  blood  is  confined  within  a 
system  of  closed  tubes,  the  bloodvessels ;  but  the  lymph,  when  first 
produced  by  transudation  through  the  walls  of  the  bloodvessels,  is  not 
enclosed  within  vessels,  but  permeates  the  tissues  or  enters  minute 
interstices  between  the  tissue-elements  surrounding  the  bloodvessels. 
Thence  it  gradually  makes  its  way  into  larger  spaces — lymph-spaces 
— which  open  into  the  thin-walled  vessels  constituting  the  radicles 
of  the  lymphatic  vascular  system.  These  smaller  lymphatic  vessels 
join  each  other  to  form  larger  tubes,  which  finally  open  into  the 
venous  portion  of  the  haematic  circulation,  thus  returning  to  the 
blood  the  lymph  which  has  made  its  way  through  the  tissues. 

The  circulating  fluids  are  kept  in  motion  chiefly  by  the  pumping 
action  of  the  heart,  which  forces  blood  into  the  arteries,  whence  it 
passes  through  the  capillaries  into  the  veins,  and  thence  back  to  the 
heart.  During  its  passage  through  the  smaller  arteries,  the  capil- 

108 


THE  CIRCULATORY  SYSTEM.  109 

laries,  and  the  smaller  veins,  a  part  of  the  plasma  of  the  blood, 
somewhat  modified  in  composition,  makes  its  way  through  the  vas- 
cular walls,  partly  by  osmosis,  partly  by  a  sort  of  filtration,  and 
becomes  the  nutrient  lymph  of  the  tissues.  The  composition  of 
this  lymph  varies  a  little  in  the  different  parts  of  the  body,  and 
this  variation  is  attributed  to  some  kind  of  activity,  allied  to  secre- 
tion, on  the  part  of  the  cells  lining  the  vessels. 

The  larger  veins  are  provided  with  pocket-like  valves,  which 
collapse  when  the  blood-current  is  toward  the  heart,  but  which  fill 
and  occlude  the  veins  when,  for  any  reason,  the  current  is  reversed. 
When,  therefore,  the  muscles  contiguous  to  the  larger  veins  thicken 
during  contraction  and  press  upon  the  veins  the  effect  is  to  urge 
the  blood  within  them  in  the  direction  of  the  heart.  This  accessory 
mode  of  propulsion  materially  aids  the  heart,  especially  during 
active  exercise,  when  the  muscles  are  in  need  of  an  abundant  supply 
of  oxygen. 

The  large  lymphatic  vessels  are  similarly  provided  with  valves, 
and  valves  guard  the  orifices  by  which  the  lymphatic  trunks  open 
into  the  veins.  But  the  chief  reason  for  the  flow  of  the  lymph 
appears  to  be  the  continuous  formation  of  fresh  lymph,  which 
drives  the  older  fluid  before  it — the  so-called  vis  a  tergo. 

For  convenient  description  we  may  divide  the  vascular  organs 
into  the  heart,  arteries,  veins,  capillaries,  and  lymphatics. 

1.  The  heart  is  covered  externally  by  a  nearly  complete  invest- 
ment of  serous  membrane,  the  epicardium,  which  is  a  part  of  the 
wall  of  the  pericardial  serous  cavity.  Its  free  surface  is  covered 
with  a  layer  of  endothelium  resting  upon  areolar  fibrous  tissue,  and 
containing  a  variable  amount  of  fat. 

The  substance  of  the  heart  is  made  up  of  a  series  of  interlacing 
and  connected  layers  of  cardiac  muscular  tissue,  separated  by  layers 
of  areolar  tissue,  which  extends  into  the  meshes  of  the  muscle,  form- 
ing the  interstitial  tissue  of  the  heart.  The  fibres  in  the  different 
layers  of  muscle  run  in  different  directions,  so  that  sections  of  the 
wall  of  the  heart  show  the  individual  muscle-cells  cut  in  various 
ways. 

The  areolar  tissue  is  more  abundant  and  denser  near  the  orifices 
of  the  heart,  and  at  the  bases  of  the  valves  merges  into  dense 
fibrous  rings,  which  send  extensions  into  the  curtains  of  the  valves, 
increasing  their  strength  and  giving  them  a  firm  connection  with 
the  substance  of  the  organ.  In  the  centre  of  the  heart,  between 


110  NORMAL  HISTOLOGY. 

the  auriculo-ventrictilar  orifices  and  the  aortic  orifice,  this  fibrous 
tissue  is  reinforced  by  a  mass  of  fibro-cartilage. 

The  cavities  of  the  heart  are  lined  by  the  endocardium,  consisting 
of  endothelium  resting  on  areolar  tissue.  The  deeper  portions  of 
the  epi-  and  endocardium  merge  with  the  areolar  tissue  of  the  body 
of  the  heart.  Smooth  muscle-fibres  are  of  occasional  occurrence  in 
the  deeper  layers  of  the  endocardium. 

The  auricles  and  the  basal  third  of  the  ventricles  contain  ganglia, 
connected  on  the  one  hand  with  the  nerves  received  by  the  heart 
from  the  cerebro-spinal  and  sympathetic  systems,  and  on  the  other 
hand  with  a  nervous  plexus  which  penetrates  the  substance  of  the 
heart  and  gives  off  minute  nervous  fibrilla?  to  the  individual  cells 
of  the  cardiac  muscle.  These  fibrillse  end  in  minute  enlargements 
connected  with  the  surfaces  of  the  muscle-cells.  Many  of  the  gan- 
glia lie  beneath  the  epicardium  or  in  the  areolar  or  adipose  tissue 
situated  in  its  deeper  portions. 

The  valves  of  the  heart  are  composed  of  fibrous  tissue,  con- 
tinuous with  that  forming  the  rings  around  the  orifices.  Their 
surfaces  are  covered  by  extensions  of  the  endocardium,  except  the 
outer  surfaces  of  the  pulmonary  and  aortic  valves,  which  are  cov- 
ered by  extensions  of  the  not  dissimilar  inner  coats  of  the  pul- 
monary artery  or  aorta.  The  fibrous  substance  of  the  valvular 
pockets  of  those  two  valves  are  further  strengthened  by  tendinous 
strips  of  fibrous  tissue  at  their  lines  of  contact  when  the  valves  are 
closed.  The  curtains  of  the  auriculo-ventricular  valves  are  also 
reinforced  by  fibrous  tissue  derived  from  fan-like  expansions  of  the 
chordae  tendinese. 

2.  The  Arteries. — It  will  be  best  to  consider  first  the  structure  of 
the  smaller  arteries,  because  the  individual  coats  are  less  complex  in 
these  than  in  the  larger  arteries. 

The  arterial  wall  consists  of  three  coats  :  the  intima,  or  internal 
coat ;  the  media ;  and  the  adventitia,  or  external  coat  (Fig.  96). 

The  intima  consists  of  three  more  or  less  well-defined  layers. 
These  are,  from  within  outward  :  1,  a  single  layer  of  endothelium  ; 
2,  a  layer  of  delicate  fibrous  tissue  containing  branching  cells ;  3,  a 
layer  of  elastic  fibrous  tissue.  The  endothelial  layer  consists  of 
cells,  usually  of  a  general  diamond  shape,  with  their  long  diago- 
nals parallel  to  the  axis  of  the  vessel  they  line.  When  the  vessel 
expands  these  cells  broaden  somewhat  and  appear  very  thin.  When 


THE  CIRCULATORY  SYSTEM. 


Ill 


the  vessel  is  contracted  they  are  thicker  and  the  portion  containing 
the  nucleus  projects  slightly  into  the  lumen  of  the  vessel. 

The  subendothelial  fibrous  tissue  forming  the  second  layer  of  the 
intima  is  composed  of  very  delicate  fibrils,  closely  packed  together, 
with  a  little  cement  between  them,  and  enclosing  irregular  spaces  in 
which  the  branching  cells  of  the  tissue  lie.  Elastic  fibres,  spring- 

FIG.  96. 


Branch  of  splenic  artery  of  a  rabbit:  a,  internal  endothelial  surface  of  the  intima;  b, 
elastic  lamina  of  the  intima  (fenestrated  membrane,  see  Fig.  59) ;  c,  media  composed 
of  smooth  muscular  tissue  encircling  the  vessel  and  therefore  appearing  in  longitudinal 
section  with  elongated  nuclei ;  d,  adventitia  of  fibrous  tissue  blending  above  and  to  the 
left  with  the  surrounding  areolar  tissue ;  e.  adipose  tissue,  between  the  cells  of  which  a 
few  lines  of  red  corpuscles  reveal  the  presence  of  capillary  bloodvessels ;  /,  small  nerve, 
containing  both  medullated  and  pale  or  non-medullated  nerve-fibres.  There  are  other 
similar  sections  of  nerves  in  the  figure.  To  the  left  of  the  artery  the  section  is  slightly 
torn,  the  adipose  tissue  being  separated  from  the  adventitia  of  the  artery.  A  few  red 
blood-corpuscles  have  been  extravasated  near  the  nerve  at  the  upper  left  corner  of  the 
figure.  There  are  also  a  few  corpuscles  within  the  lumen  of  the  artery. 

ing  from  the  external  layer  of  the  intima,  may  here  and  there, 
especially  in  the  larger  arteries,  make  their  way  into  the  subendo- 
thelial layer. 

The  elastic  lamina  of  the  intiraa  is  formed  by  a  network  of  anas- 
tomosing elastic  fibres,  having  a  general  longitudinal  disposition  with 
respect  to  the  axis  of  the  vessel.  The  spaces  left  between  the  fibres 
of  this  network  vary  considerably  in  size.  Where  they  are  small 
and  the  fibres  between  them  are  correspondingly  broad  this  layer 
has  the  appearance  of  a  perforated  membrane  (the  fenestrated  mem- 
brane of  Henle).  Even  where  this  membranous  character  of  the 
elastic  layer  is  well  developed,  elastic  fibres  are  given  off  from  its 


112 


NORMAL  HISTOLOGY. 


surfaces  and  enter  the  subendothelial  layer  on  the  one  side  and  the 
median  coat  of  the  artery  on  the  other. 

The  tunica  media,  or  middle  coat  of  the  arteries,  consists  essen- 
tially of  smooth  muscular  tissue,  with  the  cells  arranged  trans- 
versely to  the  long  axis  of  the  vessels,  so  that  by  their  contraction 
they  serve  to  diminish  the  calibre  of  the  arteries. 

The  adventitia  is  an  external  sheath  or  layer  of  fibrous   tissue 


Portion  of  a  transverse  section  of  a  human  lingual  artery  from  an  adult.  (Grunstein.> 
a,  intima ;  b,  media ;  c,  adventitia  ;  d,  endothelium ;  e,  subendothelial  stratum  (delicate 
areolar  tissue) ;  /,  tunica  elastica  interna  (fenestrated  membrane  belonging  to  the  intima) : 
g,  stratum  subelasticum  containing  elastic  fibres  (h)  that  pass  from  the  fenestrated  mem- 
brane into  the  media;  i,  concentric  elastic  fibres  within  the  media; ,;',  smooth  muscular 
fibres  of  media  with  elongated  nuclei ;  k,  white  fibrous  tissue  in  media;  I,  elastic  fibres 
radiating  from  the  media  into  the  external  elastic  tunic ;  m,  stratum  submusculare  (are- 
olar fibrous  tissue) ;  n,  tunica  elastica  externa ;  o,  stratum  elasticnm  longitudinale  (fibrous 
tissue  containing  elastic  fibres  running  parallel  with  the  axis  of  the  vessel) ;  p,  stratum 
elasticum  concentricum  (fibrous  tissue  containing  elastic  fibres  encircling  the  vessel). 
The  vasa  vasorum  supplying  the  tissues  of  the  vascular  wall  are  not  represented. 


which  merges  with  the  areolar  tissue  of  the  parts  surrounding  the 
arteries  and  serves  to  support  the  latter  without  restricting  the 
mobility  necessary  for  their  functional  activity. 


THE  CIRCULATORY  SYSTEM.  113 

In  the  larger  arteries  the  muscle-fibres  of  the  media  are  grouped 
in  bundles,  which  are  separated  by  white  and  elastic  fibrous  tissue 
(Fig.  97).  The  muscle-fibres  themselves  are  less  highly  developed 
than  in  the  smaller  arteries,  so  that  the  vessels  are  less  capable  of 
contracting,  but  are  more  highly  elastic,  because  of  the  greater 
abundance  of  elastic  fibres.  In  these  larger  arteries  the  boundary 
between  the  media  and  the  intima  is  less  sharply  defined  than 
in  the  smaller  arteries,  the  elastic  tissues  of  the  two  coats  being 
more  or  less  continuous.  In  cross-sections  of  the  smaller  arteries 
this  boundary  is  very  clearly  seen,  the  elastic  lamina  of  the  intima 
appearing  as  a  prominent  line  of  highly  refracting  material,  which 
assumes  a  wavy  course  around  the  artery  when  the  latter  is  in  a 
contracted  state.  In  such  sections  the  nuclei  of  the  endothelial 
layer  of  the  intima  appear  as  dots  at  the  very  surface  of  the  intima. 

3.  The  Capillaries  (Fig.  25). — As  the  arteries  divide  into  progres- 
sively smaller  branches  the  walls  of  the  latter  and  their  individual 
coats  become  thinner.     In  the  smallest  arterioles  the  elastic  tissue 
of  the  wall  entirely  disappears,  and  the  muscular  coat  becomes  so 
attenuated  that  it  is  represented   by  only  a  few  transverse  fibres 
partially  encircling  the  vessel.     These  in  turn  disappear,  and  the 
branches  of  the  vessel  then  consist  of  a  single  layer  of  endothelium 
continuous  with  that  lining  the  intima  of  the  larger  vessels.     These 
thinnest  and  smallest  vessels  are  the  capillaries.     They  form  a  net- 
work or  plexus  within  the  tissues,  and  finally  discharge  into  the 
smallest  veins  the  blood  they  have  received  from  the  arteries.     It 
is  chiefly  through  the  walls  of  the  capillaries  that  the  transudation 
giving  rise  to  the  lymph  takes  place,  but  some  transudation  prob- 
ably also  occurs   through    the    walls  of  the  smaller  arteries  and 
veins. 

4.  The  veins  closely  resemble  the  arteries  in  the  structure  of  their 
walls,  but  relative  to  the  size  of  the  vessel  the  wall  of  a  vein  is 
thinner  than  that  of  an  artery.     This  is  chiefly  because  the  media 
is  less  highly  developed.     The  elastic  lamina  of  the  intima  is  also 
thinner  in  veins  than  in  arteries  of  the  same  diameter. 

The  valves  of  the  veins  are  transverse,  semilunar,  pocket-like 
folds  of  the  intima,  which  are  strengthened  by  bands  of  white 
fibrous  tissue  lying  between  the  two  layers  of  intima  that  form  the 
surfaces  of  the  valves.  The  valves  usually  occur  in  pairs,  the 
edges  of  the  two  coming  into  contact  with  each  other  when  the 
valvular  pockets  are  filled  by  a  reversal  of  the  blood-current. 


114  NORMAL  HISTOLOGY. 

Behind  each  valve  the  wall  of  the  vein  bulges  slightly.  Single 
valves  of  similar  structure  not  infrequently  guard  the  orifices  by 
which  the  smaller  veins  discharge  into  those  of  larger  size. 

5.  The  Lymphatics. — The  lymph  at  first  lies  in  the  minute  inter- 
stices of  the  tissues  surrounding  the  bloodvessels  from  which  it  has 
transuded.  In  most  parts  of  the  body  those  tissues  are  varieties 
of  fibrous  connective  tissue,  and  contain  not  only  the  small  crevices 
between  their  tissue-elements,  but  larger  spaces  also,  which  have 
a  more  or  less  complete  lining  of  flat  endothelial  cells,  but  permit 
the  access  of  lymph  to  the  intercellular  interstices  of  neighboring 
tissues.  The  lymph  finds  its  way  into  these  "  lymph-spaces,"  and 
thence  into  the  lymphatic  vessels.  These  begin  either  as  a  network 
of  tubes  with  endothelial  walls,  or  as  vessels  with  blind  ends,  and 
have  a  structure  similar  to  that  of  the  blood-capillaries.  They  are 
larger,  however,  and  are  provided  with  valves.  By  their  union 
larger  vessels  are  formed,  resembling  large  veins  with  very  thin  and 
transparent  walls,  consisting  of  intima,  media,  and  adventitia. 
These  finally  unite  into  two  main  trunks,  the  thoracic  duct  and  the 
right  lymphatic  trunk,  which  open  into  the  subclavian  veins. 
Valves  are  of  much  more  frequent  occurrence  in  the  lymphatic 
vessels  than  in  the  veins,  but  their  structure  is  the  same. 

In  its  passage  through  the  lymphatic  circulatory  system  the 
lymph  has  occasionally  to  traverse  masses  of  reticular  tissue  con- 
taining large  numbers  of  lymphoid  cells,  called  "  lymph-glands." 

That  portion  of  the  lymphatic  system  which  has  its  origin  in  the 
walls  of  the  intestine  not  only  receives  the  lymph  which  transudes 
through  the  bloodvessels  supplying  that  organ,  but  takes  up  also  a 
considerable  part  of  the  fluids  absorbed  from  the  contents  of  the  in- 
testine during  digestion.  Mixed  with  this  fluid  is  a  variable  amount 
of  fat,  in  the  form  of  minute  globules.  These  globules  give  the  con- 
tents of  these  lymphatics  a  milky  appearance,  and  the  vessels  of 
this  part  of  the  lymphatic  system  have,  therefore,  received  the  name 
"  lacteals."  They  do  not  differ  essentially  from  the  lymphatics  in 
other  parts  of  the  body. 

Lymph-glands. — It  is  a  misnomer  to  call  these  structures  glands, 
for  they  produce  no  secretion.  A  better  term  is  "  lymph-nodes." 

The  lymph-nodes  are  bodies  interposed  in  the  course  of  the 
lymphatic  vessels  through  which  the  lymph-current  passes.  Their 
essential  constituent  is  lymphadenoid  tissue. 

Each  node  has  a  spherical,  ovoid,  or  reniform  shape,  with  a  de- 


THE  CIRCULATORY  SYSTEM.  115 

pression  at  one  point,  called  the  "  hilus."  It  is  invested  by  a  fibrous 
capsule,  which  is  of  areolar  character  externally,  where  it  connects 
the  node  with  surrounding  structures,  but  is  denser,  and  frequently 
reinforced  by  a  few  smooth  muscular  fibres  internally.  Extensions 
from  this  capsule  penetrate  into  the  substance  of  the  node,  forming 
"  trabeculse,"  which  support  the  structures  making  up  the  body  of 
the  node. 

The  lymphadenoid  tissue  occurs  in  two  forms  :  first,  as  spherical 
masses,  "  follicles,"  lying  toward  the  periphery  of  the  node,  except 
at  the  hilus,  and  constituting  the  "  cortex  "  (Fig.  98) ;  second,  in  the 


Single  lymph-follicle  from  a  mesenteric  node  of  the  ox.  (Flemming.)  Ib,  wide-meshed 
lymphatic  sinus  at  periphery  of  the  follicle.  Between  this  and  the  peripheral  zone  of 
the  follicle  z,  and  within  the  follicle,  the  reticulum  of  the  sinus  and  that  supporting  the 
cells  and  vessels  of  the  follicle  are  not  represented.  The  cells  are  merely  indicated  by 
their  nuclei,  the  cytoplasm  being  "omitted.  z,  peripheral  zone  of  the  follicle,  marked  by 
a  close  aggregation  of  small  lympboid  cells;  p,  more  scattered  cells  outside  of  the 
peripheral  zone  and  at  the  edge  of  the  lymph-sinus.  Within  the  zone  z  is  the  germinal 
centre  of  the  follicle,  in  which  numerous  karyokinetic  figures  are.'present,  demonstrating 
the  active  proliferation  of  the  cells  in  that  region.  Two  such  figures  are  also  represented 
within  the  lymph-sinus  at  the  upper  left  corner.  6,  bloodvessels. 

form  of  anastomosing  strands,  which  make  a  coarse  meshwork  of 
lymphadenoid  tissue  in  the  medullary  portion  of  the  node  (Fig.  99). 
The  trabeculae  springing  from  the  capsule  penetrate  the  substance 
of  the  node  between  the  follicles  in  the  cortex,  and  then  form  a  net- 
work of  fibrous  tissue  lying  in  the  meshes  of  the  medullary  lymph- 
adenoid  tissue,  after  which  they  become  continuous  with  the  mass 


116  NORMAL  HISTOLOGY. 

of  fibrous  tissue  at  the  hilus  and,  through  it,  with  the  capsule  at  that 
point. 

The  lymphatic  vessel  connected  with  the  node  divides  into  a 
number  of  branches,  the  "  afferent  vessels,"  which  penetrate  the 
capsule  at  the  periphery  and  open  into  a  wide-meshed  reticular 
tissue  lying  between  the  trabeculse  and  the  lymphadenoid  tissue  of 
the  follicles  and  the  medullary  strands.  This  more  open  reticular 
tissue,  through  which  the  lymph  circulates  most  freely,  forms  the 

FIG.  99. 


Portion  of  the  medulla  of  a  lymph-node.  (Recklinghausen.)  a,  a,  a,  anastomosing  columns 
of  lymphadenoid  tissue  ;  b,  anastomosing  extensions  of  the  cortical  trabeculse  ;  c,  lymph- 
sinus  ;  d,  capillary  bloodvessels.  The  lymphoid  cells  in  the  sinus  are  not  shown. 

"lymph-sinuses"  of  the  node,  and  is  less  densely  crowded  with 
lymphoid  cells  than  the  reticular  tissue  of  the  follicles  and  medul- 
lary lymphoid  tissue.  The  walls  of  these  sinuses,  which  are  turned 
toward  the  fibrous  tissue  of  the  trabeculse  and  their  extensions  in 
the  medulla,  are  lined  with  endothelium,  and  a  somewhat  similar,  but 
probably  much  less  complete,  lining  may  partially  separate  the 
sinuses  from  the  lymphadenoid  tissue.  However  this  may  be,  it  is 
certain  that  lymphoid  cells  can  freely  pass  from  the  lymphoid  tissue 
into  the  sinuses,  or  in  the  reverse  direction,  and  that  there  is  a  ready 
interchange  of  fluids  between  the  two. 

From  the  sinuses  the  lymph  passes  into  a  single  vessel,  the  "  effe- 
rent vessel,"  through  which  it  is  conveyed  from  the  node  at  the  hilus. 

The  arteries  supplied  to  the  lymph-node  may  be  divided  into  two- 


THE  CIRCULATORY  SYSTEM. 


117 


groups  :  first,  small  twigs  which  enter  at  the  periphery  and  are  dis- 
tributed in  the  capsule  and  fibrous  tissues  of  the  trabecuta  and  the 
medulla ;  and,  second,  arteries  which  enter  at  the  hilus,  pass  through 
the  sinuses,  and  are  distributed  in  the  lymphadenoid  tissue  of  the 
medulla  and  cortex.  The  veins  follow  the  courses  of  the  corre- 
sponding arteries.  The  nerve-supply  is  meagre,  and  consists  of  both 
medullated  and  non-medullated  fibres.  Their  mode  of  termination 
is  not  known. 

In  the  centre  of  the  follicles  the  reticular  tissue  is  more  open  and 
the  lymphoid  cells  less  abundant  than  toward  the  periphery.  Mitotic 
figures  are  of  frequent  occurrence  in  lymphoid  cells  in  this  region, 
and  it  is  evidently  a  situation  in  which  those  cells  actively  multiply. 
Further  toward  the  periphery 
the  reticular  tissue  is  closer 
and  very  densely  packed  with 
small  lymphoid  cells,  to  be- 
come more  open  again  and 
freer  of  cells  as  it  passes  into 
the  reticulum  of  the  sinus 
(Fig.  100).  This  last  reticu- 

FIG.  100. 


FIG.  101. 


Fig.  TOO.- Portion  of  lymph-follicle  from  mesentery  of  ox.  (Flemming.)  z,  peripheral  zone 
of  small,  closely  aggregated  lymphoid  cells.  To  the  right  of  these  is  a  portion  of  the 
germinal  centre  of  the  follicle,  with  larger  cells,  many  of  which  are  dividing.  Opposite 
Us  a  cell  executing  amoeboid  locomotion,  pz,  pigmented  cell,  which  has  taken  up  colored 
granules  from  outside;  tk,  dark  chromophilic  body,  the  nature  of  which  has  not  been 
determined.  Such  bodies  occasionally  occur  in  lymph-nodes,  but  their  origin  and  sig- 
nificance are  unknown. 

Fig.  101.— Section  of  a  small  portion  of  the  reticulum  of  the  sinus  in  a  human  mesenteric 
node.  (Saxer.)  6,  6,  diagrammatic  representation  of  a  portion  of  the  neighboring 
trabecula. 

lum  becomes  continuous  with   delicate   fibres  given  off  from  the 
tissues  of  the  capsule  and  trabeculse  (Fig.  101).     The  distribution 


118 


NORMAL  HISTOLOGY. 


of  the  lymphoid  cells  gives  the  follicles  a  general  concentric  appear- 


ance. 


The  lymph-follicles  of  the  cortex  not  infrequently  blend  with 
each  other,  and  the  activity  of  the  cellular  reproduction  in  their 
centres  varies  considerably  and  is  sometimes  entirely  wanting,  when 
the  concentric  arrangement  of  the  cells  disappears. 

The  structure  of  the  lymph-nodes  causes  the  lymph  entering  them 
to  traverse  a  series  of  channels,  the  "  sinuses,"  which,  in  the  aggre- 
gate, are  much  larger  than  the  combined  lumina  of  the  vessels  sup- 
plying them.  The  velocity  of  its  current  is,  therefore,  greatly  re- 
duced, and  it  remains  for  a  considerable  time  subjected  to  the  action 
of  the  lymphoid  cells  in  and  near  the  sinuses.  Small  particles  which 
may  have  gained  access  to  the  lymph  in  its  course  through  the  tis- 
sues are  arrested  in  the  lymph-nodes,  and  are  either  consumed  by 
phagocytes — i.  <?.,  cells  possessing  the  power  of  amoeboid  move- 
ment and  capable  of  incorporating  foreign  substances — or  are  con- 

FIG.  102. 


^g^ 4g/ 

xv'--— '-''" 

Section  of  red  marrow ;  human.  (Bohm  and  Davidoff.)  a,  a,  erythroblasts ;  b,  b,  myelocytes ; 
b',  myelocyte  undergoing  division  ;  c,  giant-cell  with  a  single  nucleus  ;  c',  giant-cell  with 
dividing  nucleus ;  d,  reticulum  ;  e,  space  occupied  by  a  fat-cell  (not  represented) ;  /,  gran- 
ules in  a  portion  of  an  acidophilic  cell. 

veyed  into  the  marginal  portions  of  the  follicles,  where,  if  insus- 
ceptible of  destruction,  they  remain.  It  is  in  consequence  of  this 
process  that  the  lymph-nodes  connected  with  the  bronchial  system 


THE  CIRCULATORY  SYSTEM.  119 

of  lymphatics  are  blackened  as  the  result  of  an  accumulation  of 
particles  of  carbon  that  have  been  inhaled  and  then  absorbed  into 
the  lymphatics. 

The  lymph-nodes  may,  therefore,  be  considered  as  filters  which 
remove  suspended  foreign  particles  from  the  lymph ;  but  it  is 
probable  that  the  dissolved  substances  in  the  lymph  are  also 
affected  in  its  passage  through  the  nodes,  and  that  a  purification 
of  that  fluid  is  thereby  occasioned.  A  fresh  access  of  leucocytes 
further  alters  the  character  of  the  lymph  during  its  transit  through 
the  lymph-nodes. 

Bone-marrow  (Fig.  102). — In  early  life  the  medullary  cavities  of 
the  long  bones,  as  well  as  the  cancellse  of  the  spongy  bones,  are  all 
occupied  by  that  form  of  marrow  known  as  "  red  "  bone-marrow. 
This  is  functionally  the  most  important  variety.  In  after-life  the 
marrow  in  the  medullary  cavities  of  the  long  bones  becomes  fatty 
through  infiltration  of  its  cells  with  fat,  which  converts  them 
into  cells  quite  similar  to  those  of  adipose  tissue.  Marrow  so  modi- 
fied is  called  "  yellow  "  marrow.  It  may  subsequently  undergo  a 
species  of  atrophy,  during  which  the  fat  is  absorbed  from  the  cells 
and  the  marrow  becomes  serous,  fluid  taking  the  place  of  the  mate- 
rials that  have  been  removed.  This  process  results  in  the  produc- 
tion of  a  "  mucoid  "  marrow. 

The  marrow  of  bones  possesses  a  supporting  network  of  reticular 
tissue  not  unlike  that  of  the  lymph-nodes.  In  the  meshes  of  this 
tissue  are  five  different  varieties  of  cell  (Fig.  103) :  First,  myelo- 
cytes,  cells  resembling  the  leucocytes  of  the  blood,  but  somewhat 
larger  in  size  and  possessing  distinctly  vesicular  nuclei.  They  are 
capable  of  amoeboid  movements,  and  not  infrequently  contain  gran- 
ules of  pigment  which  they  have  taken  into  their  cytoplasm. 
Second,  ery  throb  lasts,  or  nucleated  red  blood-corpuscles,  which 
divide  by  karyokinesis  and  eventually  lose  their  nuclei,  becoming 
converted  into  the  red  corpuscles  of  the  circulating  blood.  Third, 
acidophilic  cells,  containing  relatively  coarse  granules  having  an 
affinity  for  "acid"  anilin-dyes,  such  as  eosin.  These  cells  are 
larger  than  the  majority  of  the  leucocytes  circulating  in  the  blood. 
Their  nuclei  are  spherical  or  polymorphic  and  vesicular.  Fourth, 
giant-cells  with  unusually  large  bodies  and  generally  several  nuclei, 
though  occasionally  only  one  nucleus  is  present.  They  possess  the 
power  of  executing  amoeboid  movements  and  appear  to  act  as  phago- 
cytes. Where  absorption  of  bone  is  taking  place  they  are  found 


120 


NORMAL  HISTOLOGY. 


closely  applied  to  the  bone  that  is  being  removed,  and  have  in  this 
situation  been  called  "  osteoclasts."  Fifth,  basophilic  cells,  or  plasma- 
cells,  the  cytoplasm  of  which  contains  granules  having  an  affinity 


FIG.  103. 


Cells  from  bone-marrow :  a,  small  leucocyte  from  circulating  blood,  with  highly  chromatic 
nucleus  and  slight  amount  of  cytoplasm,  a  "  lymphocyte  "  probably  derived  from  a  lymph- 
node  ;  b,  b,  myelocytes,  larger  than  a,  with  vesicular  nuclei ;  c,  c,  c,  erythroblasts,  with 
nuclei  in  karyokinesis ;  c',  mature  red  corpuscle  (erythrocyte) ;  d,  acidophile  (eosinophile) 
leucocyte.  The  basophilic  leucocytes,  or  plasma  cells,  resemble  this,  but  have  smaller 
and  less  abundant  granules  of  different  chemical  nature ;  e,  giant-cell  (myeloplax)  with 
three  nuclei ;  a,  b,  c,  and  d,  from  the  marrow  of  the  fowl  (Bizzozero),  the  red  corpuscles  of 
which  are  oval  and  nucleated,  c' ;  e,  from  the  marrow  of  the  guinea-pig.  (Schiifer.) 


for  "  basic  "  anilin-dyes,  such  as  dahlia.  These  cells  are  relatively 
large,  and  possess  vesicular  and  frequently  polymorphic  nuclei. 
Aside  from  these  cells,  which  may  be  regarded  as  forming  a  part 
of  the  marrow,  it  contains  red  blood-corpuscles  and  leucocytes, 
either  formed  within  the  marrow  or  brought  to  it  by  the  circulating 
blood. 

The  functions  of  the  various  cells  in  bone-marrow  have  not  been 
finally  determined,  but  it  is  certain  that  the  erythroblasts,  by  their 
multiplication  and  transformation,  maintain  the  supply  of  red  cor- 
puscles circulating  in  the  blood. 

The  arteries  supplied  to  the  marrow  divide  freely  and  open  into 
small  capillaries,  which  appear  subsequently  to  dilate,  and  either  to 
blend  with  the  endothelial  elements  of  the  reticular  tissue  or  to 
become  pervious  through  a  separation  of  the  cells  forming  their 
walls.  In  either  case  the  blood  passes  into  the  meshes  of  the  retic- 
ular tissue,  where  it  slowly  circulates  among  the  constituents  of  the 
marrow.  It  then  passes  into  venous  radicles  devoid  of  valves,  and 
is  thence  conveyed  from  the  bone.  In  some  animals — e.  g.,  birds — 
the  production  of  red  corpuscles  appears  to  be  confined  to  the  venous 


THE  CIRCULATORY  SYSTEM. 


121 


radicles  (Fig.  104).     The  veins  leaving  the  bones  are  abundantly 
supplied  with  valves. 

FIG.  1 04. 


Section  of  small  venous  radicle  in  marrow  of  the  fowl.  (Bizzozero.)  Just  within  the  vascular 
wall  is  a  zone  of  leucocytes,  one  of  which  contains  a  karyokinetic  figure.  Within  this 
zone  is  a  second  zone  of  erythroblasts,  foururidergoing  division,  and  in  the  centre  of  the 
lumen  are  a  number  of  matured  red  blood-corpuscles  (containing  nuclei  in  the  case  of 
birds).  The  cytoplasm  of  the  leucocytes  contains  no  haemoglobin,  while  that  of  the 
erythroblasts  does.  In  birds  and,  probably,  in  other  classes  of  animals  the  marrow 
of  the  bones  is  one  of  the  sites  for  the  production  of  leucocytes  as  well  as  red  corpuscles. 
The  latter  are  not  produced  from  the  former,  but  only  from  the  erythroblasts,  which  con- 
stitute a  distinct  variety  of  cell. 

Throughout  life  the  cancellated  portions  of  the  flat  bones  and  of 
the  bodies  of  the  vertebrae  contain  red  marrow,  but  the  shafts  of 
the  long  bones  are  occupied  by  the  yellow  variety,  which  has  lost 
its  power  of  producing  red  blood-corpuscles  and  leucocytes,  and 
has,  therefore,  become  functionally  passive. 


CHAPTER  IX. 
THE  BLOOD  AND  LYMPH. 

THE  blood  consists  of  a  fluid,  the  plasma,  in  which  three  sorts 
of  bodies  are  suspended  :  the  red  corpuscles,  the  leucocytes  or 
white  corpuscles,  and  the  blood-plates. 

The  plasma  is  a  solution  in  water  of  albuminous  and  other  sub- 
stances. Some  of  these  are  of  nutritive  value  to  the  tissues  of  the 
body.  Others  have  been  received  from  those  tissues,  and  are  on 
their  way  toward  elimination  from  the  body.  Still  other  con- 
stituents have  passed  into  the  blood  from  one  part  of  the  body,  and 
are  destined  to  be  of  use  to  other  parts. 

In  the  smaller  vessels,  while  on  its  course  through  the  circulatory 
system,  portions  of  the  plasma  make  their  way  through  the  vascular 
walls  and  form  the  fluid  of  the  lymph.  This  passage  appears  to  be, 
in  part,  a  simple  filtration  through  the  walls  of  the  vessel,  or  the 
result  of  osmosis ;  in  part,  the  result  of  a  species  of  secretion 

FIG.  105. 


a  »  c 

Red  corpuscles  from  human  blood.  (Bohm  and  Davidoff.)  a,  optical  section  of  a  red  blood- 
corpuscle,  seen  from  the  edge ;  b,  surface  view.  (The  bounds  of  the  central  depression 
are  made  a  little  too  distinct  in  this  figure,  as  is  evident  from  an  inspection  of  a.)  c, 
rouleau  of  red  corpuscles.  When  undiluted  blood  has  remained  quiescent  for  a  few 
moments  the  red  corpuscles  arrange  themselves  in  such  rows,  probably  because  of  the 
attraction  which  they,  in  common  with  other  bodies  suspended  in  a  fluid  having  a  nearly 
identical  specific  gravity,  have  for  each  other. 

effected  by  the  endothelial  cells  lining  the  bloodvessels,  these  cells 
promoting  the  escape  of  certain  constituents  of  the  plasma  and 
restraining  or  preventing  that  of  others.  In  the  exercise  of  this 
secretory  function  the  endothelia  in  different  parts  of  the  vascular 
system  appear  to  act  differently,  the  composition  of  the  fluid  passing 
through  the  walls  of  the  vessels  not  being  exactly  the  same  in  all 
parts  of  the  body.  It  is  still  a  question,  however,  in  what  degree 
122 


THE  BLOOD  AND  LYMPH.  123 

the  endothelial  celLs  are  active  in  bringing  about  these  differences. 
Their  character  is  not  such  as  would  be  expected  of  cells  carrying 
on  active  processes. 

The  red  corpuscles  are  soft,  elastic  discs,  with  a  concave  impres- 
sion in  both  surfaces  (Fig.  105).  They  are  slightly  colored  by  a 
solution  of  haemoglobin,  and  are  so  abundant  that  their  presence 
gives  the  blood  an  intense  red  color ;  but  when  viewed  singly  under 
the  microscope  each  corpuscle  has  but  a  moderately  pronounced  red- 
dish-yellow tinge.  The  haemoglobin  solution  is  either  intimately 
associated  with  the  substance  composing  the  body  of  the  corpuscles, 
called  the  "  stroma,"  or  it  occupies  the  centre  of  the  corpuscle  and 
is  surrounded  by  a  pellicle  of  stroma. 

Under  normal  conditions  the  red  corpuscles,  in  man  and  most 
of  the  mammalia,  are  not  cells,  for  they  possess  no  nuclei,  nor  are 
they  capable  of  spontaneous  movement  or  multiplication.  They 
are,  rather,  cell-products,  being  formed  either  within  the  cytoplasm 
of  cells  of  mesoblastic  origin,  or  by  the  division  of  cells  derived 
from  the  mesoblast,  and  called  erythroblasts,  the  descendants  of 
which  become  converted  into  red  corpuscles  through  an  atrophy  and 
disappearance  (probably  expulsion)  of  the  nuclei  and  a  transforma- 
tion of  the  cytoplasm  into  the  stroma,  which  take  place  after  the 
elaboration  of  the  haemoglobin  within  the  cell.  The  former,  or 
intracellular,  mode  of  production  occurs  in  the  embyro,  even  before 
the  complete  development  of  the  bloodvessels ;  the  latter  mode  of 
production  seems  to  be  the  only  one  occurring  in  the  adult,  the  chief 
location  of  the  erythroblasts  appearing  to  be  in  the  red  marrow  of  the 
bones,  where  they  are  situated  either  in  the  tissues  of  the  marrow 
itself,  whence  their  descendants,  while  still  cellular,  pass  into  the 
vessels,  or  in  the  large  venous  channels  of  the  marrow,  where  the 
blood-current  is  sluggish  and  the  erythroblasts  remain  close  to  the 
vascular  walls.  In  some  anaemic  conditions  the  erythroblasts  ap- 
pear in  the  circulating  blood,  where  they  may  be  distinguished  from 
the  normal  red  corpuscles  by  the  presence  of  their  nuclei  and,  fre- 
quently, also  by  a  difference  in  size  (see  Fig.  103,  c). 

In  the  reptilia  and  birds  the  red  corpuscles  are  normally  nu- 
cleated ;  but,  though  morphologically  resembling  cells,  they  are 
incapable  of  multiplication  or  spontaneous  movement,  and  have 
undergone  such  modifications  that  they  are  not  cells  in  a  physiolog- 
ical sense. 

The  functional  value  of  the  red  corpuscles  is  dependent  upon  the 


124  NORMAL  HISTOLOGY. 

haemoglobin  they  contain,  which  is  said  to  constitute  90  per  cent,  of 
their  solid  matter.  It  is  readily  oxidized  and  reduced  again,  and 
serves  to  carry  the  oxygen  of  the  air,  obtained  during  the  passage 
of  the  blood  through  the  pulmonary  capillaries,  to  all  parts  of 
the  body.  The  red  corpuscles,  therefore,  subserve  the  respiratory 
function  of  the  blood,  as  the  plasma  subserves  its  nutritive  func- 
tion. 

The  leucocytes,  or  white  blood-corpuscles,  are  cellular  elements 
closely  resembling  the  amoeba  in  their  structure,  which  are  present 
in  the  blood  in  much  smaller  number  than  the  red  corpuscles,  the 
usual  proportion  being  about  one  to  six  hundred.  They  vary  some- 
what in  size  and  structure,  either  because  of  differences  in  their  origin, 
or  because  they  are  in  different  stages  of  development.  The  majority 
of  them  are  capable  of  ameboid  movements  ;  but  while  they  are  cir- 
culating in  the  more  rapid  currents  of  the  blood  the  constant  shocks 
they  receive  through  contact  with  other  corpuscles  or  with  the  vascu- 
lar walls  keep  their  cytoplasm  in  a  contracted  state  and  they  maintain 
a  globular  form.  If,  however,  through  any  chance  they  remain  for 
some  time  in  contact  with  the  wall  of  a  vessel,  they  are  able  to  make 
their  way  between  the  endothelial  cells  and  pass  out  of  the  circulation 
into  the  surrounding  tissues.  Here  they  creep  about,  and  for  this  rea- 
son have  been  called  the  migratory  or  wandering  cells  of  the  tissues. 
They  ultimately  either  suffer  degenerative  changes  and  disappear, 
or  find  their  way  back  into  the  circulation  through  the  lymphatic 
channels.  During  these  excursions  they  may  incorporate  stray 
particles  in  the  tissues,  and  thus  act  as  scavengers.  This  activity 
has  been  called  their  phagocytic  function,  and  may  play  an  impor- 
tant part  in  the  removal  of  material  that  should  be  absorbed  or  of 
particles  that  would  otherwise  be  injurious  to  the  tissues  ;  e.  g., 
bacteria.  (See  statements  regarding  the  nature  of  colostrum-cor- 
puscles.) 

The  emigration  of  leucocytes  from  the  bloodvessels  is  pronounced 
in  many  of  the  inflammatory  processes,  and  their  phagocytic  func- 
tion may  have  a  marked  influence  on  the  result. 

The  leucocytes  are  produced  in  the  lymphadenoid  tissues  of  the 
body,  the  lymphatic  glands,  thy m us,  spleen,  and  the  more  diffusely 
arranged  tissues  of  like  structure,  but  probably  most  abundantly  in 
the  red  marrow  of  the  bones. 

A  close  study  of  the  leucocytes  has  resulted  in  their  subdivision 
into  a  number  of  groups  according  to  their  morphological  differences 


THE  BLOOD  AND   LYMPH. 


125 


or  to  peculiarities  in  their  behavior  toward  coloring-matters.     The 
best  defined  of  these  groups  are  : 

1.  The  polynuclear  neutrophilic  leucocytes,  in  which  the  nucleus 
has  a  very  irregular  form,  often  presenting  the  appearance  of  two 
or  more  nuclei,  and  the  cytoplasm  contains  granules  that  have  an 
affinity  for  neutral  anilin-dyes  (Fig.  106,  /  and  g).  This  variety 
constitutes  about  72  per  cent,  of  the  total  number  of  leucocytes,  and 
is  probably  produced  chiefly  in  the  red  marrow  of  the  bones.  They 

FIG.  106. 


a 


Leucocytes  from  normal  human  blood.  (Bohm  and  Davidoff.)  a,  red  blood-corpuscle,  intro- 
duced for  comparison;  b,  small  mononuclear  leucocyte  (lymphocyte);  c,  large  mono- 
nuclear  leucocyte ;  g,  polynuclear  leucocyte.  These  differ  in  the  character  of  the  granules 
they  contain  (not  represented  in  the  figure).  In  normal  blood  those  granules  are  neutro- 
philic in  the  vast  majority  of  the  polynucleated  leucocytes.  Occasionally  they  are  acido- 
philic,  "esinophile  leucocytes";  sometimes  basophilic,  "  mast-cells"  or  "plasma-cells." 
d,  e,f,  intermediate  and  probably  transitional  forms  between  the  large  mononuclear  leu- 
cocytes c,  and  the  polynucleated  leucocytes,  or  leucocytes  with  polymorphic  nuclei,  g. 

possess  the  power  of  executing   amoeboid   movements  and  incor- 
porating foreign  particles. 

2.  The  lymphocytes,  with  a  single  round  nucleus  and  a  little  clear 
cytoplasm  around  it.     These  leucocytes  are  of  about  the  same  size 
as  the  red  blood-corpuscles  (Fig.  106,  b).     They  are  derived  from 
the  lymphadenoid  tissue  in  the  lymph-nodes  and  other  situations, 
and  appear  to  be  incapable  of  amoeboid  movement.    They  constitute 
about  23  per  cent,  of  the  total  number  of  leucocytes  in  normal  blood. 

3.  The  large  mononuclear  leucocytes,  which  are  larger  than  the 
red  corpuscles  and  have  oval  nuclei  surrounded  by  clear  cytoplasm 
(Fig.  106,  c).    This  variety  has  also  received  the  name  "  myelocyte," 
on  the  probably  correct  assumption  that  they  are  derived  from  the 
red  marrow  of  the  bones.     They  are  capable  of  passing  through 


126  NORMAL  HISTOLOGY. 

transitional  forms  until  they  acquire  the  characters  of  the  polynuclear 
neutrophilic  leucocytes  described  above.  The  large  mononuclear 
leucocytes,  together  with  the  transitional  forms,  make  up  about  3 
per  cent,  of  the  normal  number  of  leucocytes. 

4.  The  eosinophilic  leucocytes  (Fig.  103,  d)9  also  larger  than  the  red 
corpuscles,  with  irregular,   polymorphic    nuclei,  and   a  cytoplasm 
containing  relatively  large  granules  which  have  an  affinity  for  acid 
dyes ;  e.  g.,  eosin.     These  are  frequently  seen  in  unusual  numbers 
around  inflammatory  foci  or  in  tissues  undergoing  involution;  e. #., 
in  the  connective  tissue  of  the  breast  when  lactation  is  suspended. 
Their  significance  is  not  understood,  but  they  appear  to  be  derived 
from  the  red  bone-marrow.     They  constitute  from  1  to  2  per  cent, 
.of  the  total  number  of  leucocytes. 

5.  Basophilic  leucocytes,  occasionally  met  with,  which  are  charac- 
terized by  the  presence   of   granules  in   the  cytoplasm  having  a 
.special    affinity   for   basic    anilin-colors.       These    cells   have   also 
received  the  names  " mast-cells"  and  plasma-cells,  but  the  latter 
term  is  indefinite,  having  been   applied  to  a  number  of  cells  of 
.different  nature. 

The  blood-plates  are  colorless  round  or  oval  discs,  about  one- 
fourth  the  diameter  of  the  red  corpuscles.  Their  function  has  not 
been  definitely  determined,  but  it  is  thought  that  they  may  play  a  rdle 
in  the  production  of  fibrin,  perhaps  by  the  liberation  of  fibrin-ferment. 

Minute  globules  of  fat  are  occasionally  present  in  the  blood, 
-especially  during  digestion. 

The  lymph,  like  the  blood,  consists  of  a  fluid  portion,  the  plasma, 
and  corpuscles  held  in  suspension. 

The  plasma,  as  would  be  anticipated  from  its  origin,  is  very 
similar  in  composition  to  that  of  the  blood. 

The  corpuscles  are,  for  the  most  part,  identical  with  the  small 
leucocytes  (lymphocytes)  of  the  blood,  which  derives  its  supply  of 
those  cells  from  the  lymph  flowing  into  it. 

The  chyle  is  the  lymph  found  in  the  lacteal  lymphatics  during 
.digestion.  When  absorption  of  the  products  of  digestion  is  in 
progress  this  lymph  contains  a  great  number  of  globules  of  fat, 
£ome  so  minute  as  to  be  barely  visible  under  the  microscope.  In 
the  intervals  between  absorption  this  lymph  does  not  differ  from 
that  found  in  the  other  lymphatics  of  the  body. 

Fibrin  may  present  the  appearance  of  a  delicate  network  of  ex- 
tremely fine  fibres,  somewhat  resembling  a  cobweb  (Fig.  268),  or  these 


THE  BLOOD  AND  LYMPH.  127 

fibrils  may  be  aggregated  into  larger  threads  variously  interwoven, 
or  they  may  be  still  further  condensed  to  form  masses  of  a  hyaline 
•character.  The  fibres  may  undergo  a  disintegration  into  granules, 
Avhen  their  fibrinous  nature  is  not  readily  revealed.  Fibrin  is  not 
found  in  the  body  under  normal  conditions,  but  separates  from  the 
blood  if  the  circulation  be  arrested  for  any  considerable  length  of 
time.  It  appears  to  be  the  result  of  the  interaction  of  four  sub- 
stances :  fibrinogen,  fibrinoplastin,  fibrin-ferment,  and  salts  of  lime. 
The  latter  are  always  present  in  the  tissues;  fibrinogen  exists  in 
the  plasma  of  the  blood  and  lymph,  and  is,  therefore,  very  widely 
distributed.  The  fibrinoplastin  is  believed  to  be  derived  from  the 
bodies  of  cells  that  have  undergone  some  destructive  change ;  and 
the  ferment  may  be  derived  from  the  same  source.  These  four 
substances  are  present  when  the  flow  of  blood  through  the  ves- 
sels has  been  seriously  checked  for  a  considerable  period ;  fibrin  is 
then  formed,  causing  a  coagulation  of  the  blood.  Such  a  clot, 
within  a  vessel  during  life,  is  called  a  "  thrombus."  Coagulation 
takes  place  more  rapidly  if  there  be  a  destruction  of  tissue ;  e.  g., 
a  break  in  the  wall  of  the  vessel.  It  may  also  be  occasioned  by  a 
roughness  on  the  internal  surface  of  the  vessel,  if  the  flow  of  blood 
over  that  obstruction  is  seriously  retarded.  In  such  a  case  the 
fibrin-forming  elements  may  be  liberated  from  the  bodies  of  leuco- 
cytes that  find  lodgement  behind  the  obstruction  and  suffer  injury, 
or  they  may  be  derived  from  blood-plates  that  have  been  arrested 
and  undergone  similar  changes.  In  a  like  manner,  fibrin  may  be 
formed  in  the  lymphatic  vessels  or  the  interstices  of  the  tissues.1 

1  An  explanation  of  fibrin-formation,  offered  by  Lilienfeld,  would  serve  to 
elucidate  many  cases  of  coagulation  under  morbid  circumstances.  According  to 
this  observer,  fibrin  is  formed  by  the  union  of  "  thrombosin  "  with  calcium,  and  is, 
therefore,  a  calcium-thrombosin  compound.  The  thrombosin  is  produced  from 
fibrinogen  by  the  action  of  nuclein,  which  in  turn  is  formed  from  the  nucleohiston 
contained  in  the  nuclei  of  cells.  Coagulation,  then,  would  be  the  result  of  the 
following  process  :  the  nucleohiston  in  the  nuclei,  during  "karyolysis"  or  disintegra- 
tion of  the  nucleus,  is  decomposed  into  "  histon  "  and  nuclein.  The  latter,  acting 
,on  fibrinogen,  produces  thrombosin,  which  unites  with  calcium  to  produce  fibrin. 


CHAPTER   X. 
THE  DIGESTIVE  ORGANS. 

THE  digestive  tract  consists  of  six  hollow,  and  for  the  most  part, 
tubular  organs,  which  successively  open  into  each  other  and  extend 
from  the  pharynx  to  the  anus.  The  food,  after  mastication  and 
admixture  with  saliva  in  the  mouth,  passes  through  (1)  the  oesoph- 
agus into  (2)  the  stomach.  Here  it  undergoes  digestive  changes 
under  the  influence  of  the  gastric  secretions.  Thence  it  passes  into 
(3)  the  duodenum,  where  the  secretions  of  the  liver  and  pancreas  and 
other  glands  are  mixed  with  it  and  still  further  fit  it  for  absorption. 
From  the  duodenum  it  enters  (4)  the  small  intestine,  the  Avails  of 
which  take  up  the  available  products  of  digestion,  and  thence 
passes  into  (5)  the  colon.  In  the  latter  the  fluid  portions  are 
gradually  absorbed  and  the  relatively  dry  residue,  the  fasces,  passes 
out  of  the  body  through  (6)  the  rectum  and  the  anal  orifice. 

The  walls  of  the  digestive  organs  have  a  general  similarity  through- 
out the  whole  of  the  digestive  tract.  They  consist  of  four  coats  :  1, 
an  internal  mucous  membrane ;  2,  a  submucous  coat ;  3,  a  muscular 
coat ;  and,  4,  either  a  serous  or  a  fibrous  external  coat.  These  coats 
are,  respectively,  continuous  with  each  other  throughout  the  whole 
tract.  The  internal  coat,  or  mucous  membrane,  varies  in  both 
structure  and  function  in  the  different  organs,  and  will,  therefore,  re- 
quire closer  study  than  the  other  coats.  The  latter  have  nearly  the 
same  structure  in  all  the  organs.  The  submucous  coat  is  made  up 
of  areolar  fibrous  tissue,  which  permits  some  freedom  of  motion 
between  the  mucous  and  muscular  coats,  and  contains  the  larger 
bloodvessels  and  lymphatics  that  supply  all  the  coats.  The  mus- 
cular coat  consists,  in  general,  of  two  layers  of  smooth  muscular 
tissue  :  an  internal  circular  layer  and  an  external  longitudinal  layer. 
Its  function  is  to  produce  those  vermicular  or  peristaltic  move- 
ments which  mix  and  gradually  propel  the  food  along  the  digestive 
tract.  The  external  coat  is  smooth  and  serous  over  those  portions 
of  the  tract  which  require  the  greatest  freedom  of  motion.  It  is 
nowhere  complete,  but,  where  present,  is  really  a  portion  of  the 

128 


THE  DIGESTIVE  ORGANS. 


129 


peritoneum  which  partially  envelops  the  organs  that  are  contained 
in  the  abdominal  cavity.  Where  this  serous  covering  is  wanting 
the  external  coat  consists  of  areolar  fibrous  tissue,  which  serves  to 
connect  the  organs  of  the  digestive  tract  with  neighboring  struct- 
ures, and  thus  becomes  continuous  with  the  areolar-tissue  system 
pervading  the  whole  body.  It  supports  the  vessels  and  nerves 
which  make  their  way  through  it  to  the  different  organs. 

In  addition  to  the  organs  above  enumerated,  it  is  appropriate  to 
consider  here  the  structure  of  the  tongue,  pharynx,  salivary  glands, 
and  pancreas. 

1.  The  tongue  consists  chiefly  of  voluntary  muscles,  the  fibres  of 
which  are  grouped  in  bundles  running  in  various  directions  through 
the  substance  of  the  organ.  Between  the  individual  striated  mus- 
cle-fibres, and  also  between  the  bundles  into  which  they  are  col- 
lected, there  is  a  variable  amount  of  areolar  fibrous  tissue  contain- 
ing fat,  nerves,  and  bloodvessels  (Fig.  65).  This  areolar  tissue 
FIG.  107.  FIG.  108. 


Sections  of  papillae  of  tongue. 
Fig.  107.— Filiform  papillae ;  human.    Heitzmann.) 
Fig.  108.— Fungi  form  papillae  ;  human.    (Heitzmann.) 
E,  stratified  epithelium;  C,  injected  capillaries  within  the  fibrous  tissue  of  the  papillae; 

L,  lymphadenoid  tissue  in  lower  portion  of  mucous  membrane ;  M,  muscular  tissue  of 

the  tongue. 

is  more  abundant  near  the  surface  of  the  tongue,  and  is  covered 
with  a  layer  of  stratified  epithelium,  thicker  at  the  sides  and  on  the 
dorsum  of  the  tongue  than  on  its  under  surface,  where  it  becomes 

9 


130 


NORMAL  HISTOLOGY. 


continuous  with  the  stratified  epithelium  covering   the  gums  and 
lining  the  buccal  cavity. 

FIG.  109. 
& 


Two  circumvallate  papillse  ;  rabbit.  (Ranvier.)  p,  pf,  fibrous  tissue  extending  into  the  papilla  ; 
p',  that  containing  the  nerves  passing  to  the  taste-buds  ;  g,  taste-buds ;  v,  small  vein ;  n,  n, 
nerves  ;  a,  acini  of  a  serous  gland. 

The  upper  surface  and  the  edges  of  the  tongue  are  covered  with 
papillae,  some  of  which  are  pointed  (filiform  papillae),  others  rounded 

FIG.  110. 


Portion  of  a  section  of  a  mucous  gland  in  the  human  tongue.  (Benda  and  Guenther's  Atlas.) 
a,  duct ;  b,  acinus  opening  into  a  duct-radicle ;  c,  acinus  lined  with  mucigenous  cells,  sim- 
ilar to  b.  Between  and  below  a  and  c,  cross-section  of  a  small  artery,  recognizable  by  the 
elongated  nuclei  of  its  muscular  coat. 

(fungiform  papillae),  and  still  others  surrounded  by  a  sulcus  (cir- 
cumvallate papilla)  (Figs.  107-109).    Within  the  epithelium  lining 


THE  DIGESTIVE  ORGANS.  131 

this  sulcus  are  peculiar  groups  of  cells,  called  taste-buds,  which  will 
be  described  in  a  subsequent  chapter.  At  the  junction  of  the 
middle  and  posterior  thirds  of  the  upper  surface  of  the  tongue 
there  are  several  of  these  circumvallate  papillae  which  are  of 
unusual  size. 

Within  the  subepithelial  areolar  tissue,  and  often  extending  for 
some  distance  between  the  muscles,  there  are,  here  and  there,  small 
racemose  glands,  which  secrete  a  serous  or  mucous  fluid  (Figs.  109,  a 
and  110).  They  are  most  abundant  on  the  back  and  sides  of  the  pos- 
terior part  of  the  tongue,  and  their  ducts  frequently  open  into  the  sulci 
of  the  circumvallate  papilla?.  Within  the  subepithelial  areolar  tissue 
small  collections  of  lymphadenoid  tissue  (lymph-follicles)  are  also  of 
not  infrequent  occurrence.  The  papilla?  covering  these  are  low  and 
inconspicuous,  so  that  the  surface  of  the  tongue  appears  unusually 
smooth  at  those  points. 

2.  The  salivary  glands  belong  to  the  racemose  variety  of  secreting 
glands.  The  secretions  which  they  furnish  are  of  two  kinds :  1,  a 
thin,  serous  fluid,  containing  albuminoid  materials,  among  which  are 
the  specific  ferments  elaborated  by  the  gland ;  and,  2,  a  viscid  fluid 
containing  mucin.  These  two  secretions  are  furnished  by  acini  lined 
with  different  varieties  of  epithelium.  The  parotid  gland  secretes 
only  the  serous  fluid,  and  is  composed  of  serous  alveoli.  The  sub- 
lingual  gland  secretes  only  the  mucous  fluid ;  but  the  submaxillary 
gland  secretes  both,  and,  therefore,  contains  both  serous-  and 
mucous-secreting  cells. 

The  cells  which  line  the  mucous  acini  have  clear  bodies,  as  the 
result  of  a  storage  of  transparent  globules  of  mucin  or  mucigen 
within  the  cytoplasm.  Where  these  globules  are  abundant  the 
nuclei  of  the  cells  are  crowded  toward  the  attached  ends  of  the 
cells.  When  the  mucin  is  discharged  from  the  cells  they  become 
smaller,  less  clear,  and  more  granular  in  appearance. 

At  the  periphery  of  the  acini,  and  especially  well  marked  at  or 
near  their  blind  extremities,  are,  here  and  there,  crescentic,  granular 
epithelial  cells,  which  may  reach  the  lumen  of  the  acinus  or  be 
crowded  back  by  the  enlarged  cells  adjoining  them.  These  cells 
form  the  "  crescents  of  Gianuzzi."  In  the  submaxillary  gland,  at 
least,  many  of  these  crescents  secrete  the  serous  or  albuminoid  fluid 
mentioned  above.  This  secretion  reaches  the  lumen  of  the  gland 
through  minute  intracellular  channels  (Fig.  111). 

The  serous  alveoli  of  the  salivary  glands  are  lined  with  cells  that, 


132 


NORMAL  HISTOLOGY. 


at  certain  stages  of  their  activity,  are  so  crowded  with  granules  that 
the  nuclei  are  obscured.  These  granules  are  the  accumulated  mate- 
rial from  which  the  secretion  is  formed,  and  when  the  gland  has 
been  functionally  active  for  some  time  they  diminish  in  number, 


FIG.  111. 


Section  of  an  acinus  of  the  human  submaxillary  gland.  (Krause.)  The  lumen  is  surrounded 
by  mucous  cells,  containing  globules  of  mucigen.  Two  groups  of  Gianuzzi's  crescents  are 
represented,  with  the  intracellular  channels  conveying  the  serous  secretion  to  the  lumen. 

and  the  nuclei  then  come  into  view.  At  the  same  time  the  cells 
become  smaller,  and  the  lumen  within  the  acinus,  which  at  first  was 
barely  distinguishable,  becomes  more  obvious. 

The  epithelium  lining  the  acini  of  all  the  salivary  glands  rests 

FIG.  112. 


Diagrammatic  representation  of  a  portion  of  a  human  submaxillary  gland.  (Krause.)  a,  duct, 
lined  with  columnar  cells,  striated  at  their  bases  and  passing  into  a  more  cubical  epithe- 
lium without  such  striation  ;  &,  mucous  cells ;  c,  serous  cells ;  d,  crescent ;  e,  basement- 
membrane.  In  this  figure  the  convoluted  course  of  the  ducts  and  tubular  acini  has  been 
ignored,  and  they  have  been  represented  as  though  lying  in  a  single  plane. 

upon  a  modified  connective  tissue,  called  the  "  basement-membrane," 
which  consists  of  flattened  cells  arranged  to  form  a  broad,  mem- 
branous reticulum,  the  meshes  of  which  are  filled  with  cement. 
Outside  of  this  basement-membrane  there  is  a  small  amount  of 


THE  DIGESTIVE  ORGANS. 


133 


vascular  areolar  tissue,  and  broader  bands  of  that  tissue  divide  the 
whole  gland  into  small  lobes  and  these  again  into  still  smaller 
lobules  (Fig.  25). 

The  ducts  of  the  salivary  glands  are  lined  with  columnar  or  pyram- 
idal epithelial  cells,  the  attached  ends  of  which  often  show  a  stria- 


FIG.  113. 


Part  of  a  cross-section  of  the  oesophagus  of  a  dog.  (Bohm  and  Davidoff.)  a,  mucous  mem- 
brane ;  6,  submucous  coat ;  c,  muscular  coat ;  d ,  fibrous  coat ;  e,  stratified  epithelium ;  /, 
subepithelial  areolar  tissue  (sometimes  called  the  "  tunica  propria  "  of  the  mucous  mem- 
brane) ;  g,  muscularis  mucosse;  h,  areolar  tissue  of  the  submucosa,  containing  the  chief 
branches  of  the  arterial  and  venous  vessels;  i,  internal,  encircling  layer  of  the  muscular 
coat.  It  is  the  contraction  of  this  coat  that  has  caused  a  longitudinal  wrinkling  of  the 
mucous  membrane.  One  of  those  folds  is  completely  and  two  are  partially  shown,  j, 
external,  longitudinal  layer  of  the  muscular  coat ;  k,  areolar  tissue  forming  the  external 
coat  and  connecting  the  oesophagus  with  neighboring  structures.  A  few  large  vessels 
entering  the  oesophagus  are  represented  in  this  coat. 

tion  perpendicular  to  the  surface  of  the  basement-membrane  (Fig. 
112). 

The  nerves  ramify  in  the  interlobular  areolar  tissue  and  send 
delicate,  non-medullated  fibres  through  the  basement-membrane  to 
be  distributed  upon  and  between  the  epithelial  cells.  Occasionally 
small  ganglia  are  seen  upon  the  larger  nerves. 


134  NORMAL  HISTOLOGY. 

3.  The  (Esophagus  (Fig.   113). — The  mucous  membrane  of  the 
oesophagus  is  composed  of  three  layers.     The  innermost  layer  is 
made  up  of  stratified  epithelium.     Beneath  this  is  a  layer  of  fibrous 
tissue,  with  small  papillae  extending  into  the  deeper  portions  of  the 
epithelium  (see  Fig.  38).     Outside  of  this  is  a  layer  of  longitudinal 
smooth  muscular  tissue,  the  "muscularis  mucosse."     This  is  but 
imperfectly  represented  at  the  upper  part  of  the  oesophagus,  but  at  the 
lower  end  forms  a  continuous  layer  separating  the  "  tunica  propria  " 
(Fig.  113, /)  of  the  mucous  membrane  from  the  submucons  coat,  and 
becoming  continuous  with  a  similar  layer  of  smooth  muscular  tissue 
in  the  mucous  membrane  of  the  stomach  and  intestine.     Occasion- 
ally small,  imperfectly  defined  lymph-follicles  are  met  with  in  the 
mucous  membrane. 

The  submucous  coat  of  loose  areolar  tissue  contains  small  race- 
mose glands  sparsely  distributed  through  it,  the  ducts  of  which 
penetrate  the  mucous  membrane  and  open  upon  the  internal  surface 
of  the  oesophagus. 

The  muscular  coat  consists  of  an  internal  circular  and  an  external 
longitudinal  layer,  which  at  the  upper  end  of  the  oesophagus  are 
composed  of  striated  muscle.  This  is  gradually  replaced  by  smooth 
muscular  tissue  further  down  the  oesophagus,  and  at  its  lower  end 
only  the  latter  tissue  is  found. 

The  external  coat  of  the  oesophagus  is  represented  by  a  variable 
amount  of  areolar  tissue  which  loosely  connects  it  with  the  sur- 
rounding structures. 

4.  The    Stomach. — Nearly  the  whole  thickness    of   the   mucous 
membrane  of  the  stomach  is  made  up  of  straight  tubular  glands 
(gastric  tubules),  which  lie  perpendicular  to  the  surface,  and  are 
separated  from  each  other  by  only  a  small  amount  of  a  delicate, 
highly  vascular  areolar  tissue.     This  is  a  little  denser  and  more 
abundant  below  the  deep  ends  of   the  glands,  where  it  separates 
them  from  the  muscularis  mucosse  forming  the  deepest  layer  of  the 
mucous  membrane. 

The  mouths  of  the  gastric  tubules  open  into  shallow,  polygonal 
depressions  or  crypts  on  the  surface  of  the  mucous  membrane, 
several  glands  opening  into  each  depression.  These  depressions 
give  the  internal  surface  of  the  stomach  a  reticular  appearance  when 
viewed  with  a  low  power.  They,  and  the  ridges  which  separate 
them,  are  covered  with  a  rather  tall  columnar  epithelium.  The 
glands  which  open  into  them  are  of  two  kinds :  the  "  pyloric " 


THE  DIGESTIVE  ORGANS. 


135 


FIG.  115. 


FIG.  114. 


...% 


Fig.  114.— Vertical  section  through  mucous 
membrane  of  pyloric  end  of  stomach ; 
human.  (Bohm  and  Davidoff.)  a,  co- 
lumnar epithelium  covering  surface  of 
mucous  membrane;  6,  crypt  lined  with 
somewhat  lower  columnar  epithelium; 
c,  gastric  tubules;  d,  tunica  propria, 
somewhat  lymphoid  in  character ;  e,  mus- 
cularis  mucosse,  of  smooth  muscular 
tissue. 

Fig.  115. — Nearly  vertical  section  of  the  mucous  membrane  near  the  cardiac  end  of  the  stom- 
ach ;  rabbit :  a,  columnar  epithelium  covering  the  surface  of  the  mucous  membrane ; 
6,  that  lining  a  crypt ;  c,  duct ;  d,  parietal  cell  extending  to  the  lumen  of  the  gland : 
e,  lumen,  readily  traced  for  only  a  short  distance;/,  central  or  chief  cells;  g,  small 
artery,  to  the  left  and  above  it,  a  small  vein ;  h,  muscularis  mucosfe,  consistiug  of  three 
thin  layers  of  smooth  muscular  tissue,  the  middle  layer  in  transverse,  the  others  in 
longitudinal  section ;  i,  portion  of  submucosa.  The  specimen  was  taken  from  an  animal 
some  time  after  the  ingestion  of  food,  and  the  chief  cells  are,  in  consequence,  relatively 
small  in  comparison  with  the  size  of  the  parietal  cells. 


136 


NORMAL  HISTOLOGY, 


variety,  so-called  because  more  abundant  at  the  pyloric  end  of  the 
stomach,  and  the  "cardiac77  variety,  which  preponderate  near  the 
cardiac  end. 

The  pyloric  glands  (Fig.  114)  have  the  simpler  structure.  They 
possess  a  comparatively  deep  and  open  mouth,  lined  with  columnar 
epithelial  cells  similar  to  and  continuous  with  those  lining  the  de- 
pressions already  mentioned,  and,  like  them,  mucigenous.  Into 
these  mouths  one  or  more  straight  tubular  glands,  lined  with  low, 
granular  columnar  cells,  discharge  their  secretion. 

The  cardiac  glands  (Fig.  115)  have  shallower  mouths  than  the 
pyloric  glands,  and  the  tubes  that  open  into  them  contain  two  sorts 
of  epithelial  cells  :  1,  the  "  chief7'  or  central  cells,  which  line  and 
nearly  fill  the  whole  tubule,  leaving  only  a  very  small  and  some- 
what tortuous  lumen  in  the  centre ;  and,  2,  the  parietal  cells,  lying 
at  intervals  between  the  central  cells  and  the  surrounding  connective 
tissue,  but  sometimes  projecting  between  two  central  cells  nearly 
or  quite  to  the  lumen  of  the  gland.  Very  fine  channels  run  from 
that  lumen  to  and  around  these  parietal  cells,  which  are  believed  to 
produce  the  free  acid  of  the  gastric  juice  (Figs.  116-118). 


FIG.  116. 


FIG.  117. 


FIG.  118. 


Cross-sections  of  gastric  glands ;  dog.    (Hamburger.) 

Figs.  116  and  117.— From  the  cardiac  end  of  the  stomach,  showing  the  chief  or  central  cells 
and  the  parietal  cells.  116,  from  a  dog  killed  during  the  second  hour  of  digestion.  The 
central  cells  are  relatively  large,  and  the  lumen  is  reduced  to  a  mere  line,  appearing  as 
a  dot  in  the  centre  of  the  cross-section.  117,  from  a  dog  killed  during  the  seventh  hour  of 
digestion.  The  parietal  cells  are  relatively  large,  and  the  lumen  more  distinct  than  in 
116,  owing  to  loss  of  material  on  the  part  of  the  central  cells  and  a  gain  on  the  part  of  the 
parietal  cells.  One  of  the  latter  is  in  communication  with  the  lumen  through  a  small 
channel  between  the  central  cells. 

Fig.  118.— From  the  pyloric  end  of  the  stomach  during  the  fifth  hour  of  digestion.  The  cells 
6  have  parted  with  their  secretion  and  are  compressed  by  the  cells  a,  which  still  retain 
the  materials  stored  for  secretion.  The  lumen  of  the  gland  is  much  larger  than  that  of 
the  glands  at  the  cardiac  end  of  the  stomach. 

Besides  the  secreting  glands,  the  mucous  membrane  of  the  stom- 
ach sometimes  contains  small  lymph-follicles.  Its  blood-  and 
lymph-supplies  are  abundant,  and  nerves  are  distributed  to  its 
various  tissue-elements. 


THE  DIGESTIVE  ORGANS.  137 

The  deepest  layer  of  the  mucous  membrane  is  the  muscularis 
mucosse,  made  up  of  two  or  three  strata  of  smooth  muscular  tissue 
in  which  the  fibres  run  in  different  directions. 

The  submucous  coat  of  the  stomach  consists  of  loose  areolar  tissue, 
which  allows  considerable  freedom  of  motion  between  the  mucous 
membrane  and  the  muscular  coat.  When,  therefore,  the  organ  is 
empty  the  contraction  of  the  muscular  coat  throws  the  mucous 
membrane  into  coarse  folds  (rugae).  The  large  arteries,  veins,  and 
lymphatics  course  in  this  submucous  tissue,  and  thence  send  branches 
into  both  the  mucous  and  muscular  coats.  The  nerves  also  form  a 
ganglionated  plexus  in  this  coat. 

The  muscular  coat  consists  of  an  external  longitudinal  layer, 
inside  of  which  is  another  layer  encircling  the  organ.  The  external 
layer  is  continuous  with  the  outer  muscular  layer  of  the  oesophagus. 
The  internal  muscular  layer  of  the  latter  organ  is  continued  into  the 
wall  of  the  stomach  as  a  scattered  set  of  oblique  fibres  lying  internal 
to  the  encircling  fibres  already  mentioned.  The  muscular  coat  of  the 
stomach  may,  therefore,  be  considered  as  composed  of  three  layers, 
the  innermost  of  which  is  incomplete.  At  the  pylorus  the  encircling 
muscular  layer  is  thickened. 

Aside  from  the  fibrous  tissue  that  more  or  less  completely  sepa- 
rates its  layers,  the  muscular  coat  contains  ganglionated  nerve- 
plexuses. 

The  external  surface  of  the  stomach  is  covered  with  a  serous  in- 
vestment of  peritoneum,  except  along  the  curvatures,  where  the 
peritoneum  is  reflected  from  the  organ,  permitting  the  passage  of 
its  vessels  and  nerves. 

5.  The  Duodenum. — The  structures  characteristic  of  the  small 
intestine  first  make  their  appearance  in  the  duodenum.  We  shall 
first  consider  those  features  which  are  found  throughout  the  small 
intestine,  and  then  describe  those  which  are  peculiar  to  the  duod- 
enum (Fig.  119). 

The  mucous  membrane  presents  thin,  transverse  folds,  the  val- 
vulse  conniventes,  which  are  not  obliterated  when  the  intestinal  wall 
is  stretched.  They  are  made  up  of  a  thin  layer  of  areolar  tissue, 
extending  from  the  submucous  coat  of  the  intestine,  which  is  cov- 
ered on  both  surfaces  with  mucous  membrane.  This  arrangement 
serves  greatly  to  increase  the  surface  of  mucous  membrane  coming 
in  contact  with  the  contents  of  the  intestine,  a  provision  facilitating 
absorption  of  the  products  of  digestion. 


138 


NORMAL  HISTOLOGY. 


The  valvulse  conniventes  begin  a  short  distance  below  the  pylorus, 
and  are  very  numerous  and  prominent  in  the  duodenum,  but  become 
progressively  less  frequent  and  pronounced  in  the  lower  portions  of 
the  small  intestine. 

The  absorbent  surface  of  the  small  intestine  is  still  further  in- 


FIG.  119. 


Diagram  representing  the  structure  of  the  human  small  intestine.  (Bohm,  Davidoff,  and 
Mall,  slightly  modified.)  Two  villi  are  represented.  In  the  one  on  the  left  the  blood- 
vessels are  shown  ;  in  the  one  on  the  right,  the  lymphatics.  The  line  S  indicates  the  sur- 
face of  the  mucous  membrane  between  the  villi.  a,  central  lacteal  vessel ;  b,  smooth 
muscular  fibres  extending  into  the  villus  from  the  muscularis  mucosse :  c,  lymphadenoid 
tissue  beneath  the  epithelial  covering  of  the  villus ;  d,  crypt  of  Lieberkiihn ;  e,  tunica 
propria  of  lymphadenoid  tissue,  and  continuous  with  that  of  the  villus ;  /,  muscularis 
mucosae,  forming  the  deepest  portion  of  the  mucous  membrane ;  g,  submucosa  containing 
the  larger  bloodvessels  and  the  lymphatic  plexus  h;  i,  encircling  layer  of  the  muscular 
coat ;  j,  longitudinal  layer ;  k,  lymphatic  plexus  within  the  muscular  coat ;  I,  serous  coat ; 
TO,  vein.  The  crypts  are  lined,  and  the  villi  covered,  with  columnar  epithelium. 

creased  by  the  presence  of  innumerable  minute,  finger-like  projec- 
tions from  the  surface  of  the  mucous  membrane,  the  villi.  These 
are  just  discernible  by  the  unaided  eye,  and  give  the  internal  surface 
of  the  intestine  a  velvety  appearance. 


THE  DIGESTIVE  ORGANS.  139 

Between  the  attached  ends  of  the  villi,  and  opening  upon  the  sur- 
face of  the  mucous  membrane,  are  tubular  depressions  extending 
nearly  to  the  muscularis  mucosse.  These  are  the  "  crypts  of  Lieber- 
kiihn,"  and  have  the  appearance  of  simple  tubular  glands ;  but  it  is 
doubtful  if  they  elaborate  any  peculiar  secretion.  These  crypts  are 
present,  not  only  in  the  whole  extent  of  the  small  intestine,  but 
also  throughout  that  of  the  colon. 

The  crypts  of  Lieberkuhn  are  lined  with  columnar  epithelium, 
which  also  covers  the  surface  of  the  mucous  membrane  and  the  villi 
springing  from  it.  The  cells  composing  this  epithelium  multiply  in 
the  crypts,  and,  as  they  mature,  are  gradually  moved  toward  their 
orifies,  whence  they  replace  those  that  have  been  destroyed  upon  the 
surfaces  of  the  villi.  The  cells  possess  a  granular  cytoplasm,  which 
becomes  infiltrated  with  fat  during  digestion  ;  an  oval,  vesicular 
nucleus  ;  and  a  delicate  cell-membrane.  The  free  ends  of  the  cells 
are  formed  by  a  well-marked  cuticle,  which  may  be  either  homo- 
geneous in  appearance,  or  present  very  fine  vertical  striations  (Fig. 
37).  Many  of  the  cells  are  mucigenous  and  contain  globules  of  mucus 
near  their  free  ends,  or  appear  as  goblet-cells  after  the  discharge  of 
that  secretion.  These  cells  are  more  abundant  on  the  villi,  where 
they  are  older,  than  in  the  crypts  lined  with  less  mature  cells. 

The  epithelium  rests  upon  a  basement-membrane,  which  contains 
nuclei,  and  is  therefore  composed,  in  part  at  least,  of  cells.  Beneath 
this  basement-membrane  is  a  layer  of  reticular  and  areolar  tissues, 
containing  a  variable  number  of  lymphoid  cells  and  numerous 
capillary  bloodvessels.  The  rest  of  the  mucous  membrane,  down 
to  the  muscularis  mucosaB,  and  the  axes  of  the  villi  are  occupied  by 
areolar  fibrous  tissue. 

The  thin  muscularis  mucosaB,  which  forms  the  deepest  layer  of 
the  mucous  membrane,  is  made  up  of  two  layers  of  smooth  muscular 
tissue  :  an  internal  layer,  in  which  the  fibres  run  transversely  to  the 
axis  of  the  intestine,  and  an  external  longitudinal  layer.  From  the 
upper  surface  of  this  muscular  layer  of  the  mucous  membrane 
muscular  fibres  extend  into  the  villi,  in  the  areolar  tissue  in  their 
axes,  and  serve  to  shorten  the  villi  by  their  contraction,  so  that  the 
villi  are  moved  about  in  the  intestinal  contents  during  the  process 
of  absorption.  In  the  centre  of  each  villus  is  a  capillary  lymphatic 
vessel  arising  in  a  blind  extremity  near  the  apex  of  the  villus. 
These  lymphatics  open  into  a  lymphatic  plexus  situated  between  the 
muscularis  mucosse  and  the  ends  of  the  crypts  of  Lieberkuhn,  and 


140  NORMAL  HISTOLOGY. 

thence  discharge  their  contents  into  the  lymphatics  in  the  sub- 
mucosa.  The  muscular  fibres  in  the  villi  probably  aid  in  the  pro- 
pulsion of  the  chyle  in  these  lymphatics  (Fig.  120). 


FIG.  120. 


- 


Axial  section  of  villus  of  the  dog.  (Kultschitzky.)  a,  epithelial  covering  with  cuticle  ;  b, 
goblet-cell ;  c,  space  between  tapering  ends  of  the  epithelial  cells ;  d,  cell  of  the  base- 
ment-membrane ;  e,  smooth  muscular  fibres ;  /,  reticulum  of  the  tunica  propria  (the 
lymphoid  celjs  have  been,  for  the  most  part,  removed) ;  g,  lumen  of  the  central  lymphatic 
The  bloodvessels  are  not  represented. 

The  submucous  coat  of  the  intestine  is  composed  of  areolar  fibrous 
tissue.  Outside  of  this  coat  is  the  muscular  coat,  divisible  into  two 
layers,  which  is  covered  throughout  the  whole  circumference  of  the 
intestine,  except  at  the  line  of  mesenteric  attachment,  with  a  serous 
investment  of  the  peritoneum. 

In  the  duodenum  the  submucous  coat  contains  compound  tubular 
glands,  the  glands  of  Brunner,  the  ducts  from  which  penetrate  the 
muscularis  mucosse  and  open  upon  the  surface  of  the  mucous  mem- 
brane, between  the  crypts  of  Lieberkiihn.  Here  and  there,  in  the 
duodenum,  are  little  collections  of  lymphadenoid  tissue,  occupying 
an  enlarged  villus  and  often  extending  through  the  muscularis 
mucosse  into  the  submucous  areolar  tissue  (Fig.  121).  These 


THE  DIGESTIVE  ORGANS. 


141 


lymph -follicles  may  be  regarded  as  the  result  of  an  increase  in  the 
amount  of  reticular  tissue  of  the  villus,  which  has  replaced  the 
other  structures  usually  present.  In  the  lower  portions  of  the 
small  intestine  there  are  collections  of  these  solitary  follicles, 
which  have  received  the  name  u  Peyer's  patches.7' 

6.  The  small  intestine  below  the  duodenum  resembles  the  latter 


FIG.  121. 


Section  of  solitary  follicle  from  the  ileum.  (Cadiat.)  a,  space  left  by  the  disintegration  of 
the  central,  delicate  lymphadenoid  tissue  of  the  follicle  during  the  preparation  of  the  sec- 
tion ;  b,  columnar  epithelium  of  intestinal  surface ;  c,  c,  villi,  partially  denuded  of  epithe- 
lium; d,  crypt;  e,f,  muscularis  mucosae;  above  /,  the  point  where  the  vessels  enter  the 
follicle.  The  Peyer's  patches  are  collections  of  such  solitary  follicles,  placed  side  by  side 
and  destitute  of  villi  at  their  upper  surfaces. 

in  structure,  with  a  few  modifications,  which  become  progressively 
more  marked  as  the  distance  from  the  stomach  increases. 

The  glands  of  Brunner  are  most  abundant  near  the  upper  part 
of  the  duodenum,  more  sparsely  distributed  further  down,  and 
usually  disappear  entirely  before  the  beginning  of  the  jejunum. 

The  valvulse  conniventes,  which  are  most  highly  developed  a 
little  below  the  entrance  of  the  gall  and  pancreatic  ducts,  also 
become  lower  and  less  frequent  along  the  course  of  the  intestine, 
and  finally  disappear  about  the  middle  of  the  ileum. 

The  crypts  of  Lieberkiihn  are  deepest  in  the  upper  part  of  the 
intestinal  tract,  but  persist  in  shallower  form  throughout  its  whole 
extent,  as  well  as  along  the  whole  length  of  the  colon. 


142  NORMAL  HISTOLOGY. 

The  Peyer's  patches  are  most  abundant  in  the  lower  part  of  the 
ileum,  where  they  lie  in  the  intestinal  wall  opposite  the  line  of 
mesenteric  attachment,  and  form  oval  areas  with  their  long  axes 
parallel  to  the  axis  of  the  intestine. 

7.  The  Colon. — The  mucous  membrane  of  the  colon  is  destitute 
of  villi,  but  contains  crypts  of  Lieberkiihn  closely  arranged  side  by 
side  and  lined  with  columnar  epithelium  rich  in  mucigenous  cells. 
The  muscularis  mucosse  is  similar  to  that  of  the  small  intestine,  and 
gives  oif  occasional  fibres  that  penetrate  between  the  crypts. 

The  submucous  coat  resembles  that  of  the  small  intestine,  and,  in 
common  with  the  mucous  membrane,  contains  solitary  lymph-fol- 
licles, most  abundantly  in  the  csecum  and  vermiform  appendix. 

The  muscular  coat  has  its  outer  or  longitudinal  layer  most  highly 
developed  in  three  bands,  which  are  situated  about  equidistantly 
around  the  circumference  of  the  bowel  and  occasion  a  pouching  of 
the  intervening  wall. 

The  serous  coat  is  similar  to  that  of  the  small  intestine,  but  is 
occasionally  extended  over  small  pendulous  projections  of  the 
subserous  fibrous  tissue,  which  contain  adipose  tissue,  appendices 
epiploicse. 

8.  The  rectum  resembles  the  colon  in  its  structure,  except  that  the 
three  muscular  bands  present  in  the  latter  are  wanting.    The  mucous 
membrane  as  it  passes  into  the  anal  canal  loses  its  tubular  glands, 
and   subsequently  becomes  covered,  not  with  columnar,  but  with 
stratified   epithelium,  continuous  with   the  epidermis  of  the   skin 
around  the  anus. 

9.  The  pancreas  (Fig.  122)  has  a  structure  similar  to  that  of  the 
.salivary  glands,  but  its  lobules  are  separated  and  held  in  place  by  a 
rather  more  considerable  amount  of  loose  areolar  tissue,  in  which 
there  are  occasional  groups  of  cells  of  uncertain  nature,  but  cer- 
tainly distinct  from   those   lining  the  glandular  acini.     They  are 
.called  the  "  interalveolar  cell-islets,"  and  may,  perhaps,  be  of  the 
nature  of  ductless  glands  (q.  v.). 

As  the  pancreas  exercises  its  secretory  function  the  granules 
within  its  cells  move  toward  the  lumina  of  the  acini  and  successively 
.disappear,  the  attached  ends  of  the  cells  becoming  clearer  and  the 
whole  cell  diminishing  somewhat  in  size  during  the  process. 

The  nerves  of  the  stomach  and  intestinal  tract  form  two  gan- 
glionated  plexuses,  the  plexus  of  Auerbach,  which  lies  between  the 
two  layers  of  the  muscular  coat,  and  the  plexus  of  Meissner,  situ- 


THE  DIGESTIVE  ORGANS. 


143 


ated  in  the  submucous  coat.  From  these  plexuses  fibres  are  dis- 
tributed to  the  muscles  and  other  structural  elements.  These  fibres 
are  of  the  non-medullated  variety. 

The  nerves  of  the  pancreas  are  also  non-medullated,  possess  a 
few  ganglia  within  the  organ,  and  are  finally  distributed  among  the 
epithelial  cells. 

The  Tonsils,  Lymph-follicles,  and  Peyer's  Patches. — These  collec- 
tions of  lymphadenoid  tissue  in  the  alimentary  tract  have  special 

FIG.  122. 


.-Section  of  human  pancreas.  (Bohm  and  Davidoff.)  a,  larger  duct ;  b,  beginning  of  duct ;  c,  d, 
acini  with  cells  belonging  to  the  corresponding  duct-radicles  in  their  centers ;  e,  acinus, 
cut  just  beyond  the  lumen ;  /,  interalveolar  cell-group  (?) ;  g,  fibrous  connective  tissue, 
forming  the  interstitial  tissue  of  the  organ. 

interest  to  the  physician  as  being  points  particularly  liable  to  infec- 
tion. The  solitary  follicles  of  the  stomach  and  of  the  small  and 
large  intestine,  and  the  collections  of  such  follicles  forming  the 
patches  of  Peyer,  are  the  sites  which  are  most  vulnerable  to 
invasion  by  pathogenic  bacteria  in  the  digestive  tract,  though  they 
are  probably  protected  to  a  considerable  extent  by  the  germicidal 
powers  of  the  acid  gastric  juice.  This  is  not  always  capable  of 
guarding  them  from  infection  by  the  typhoid  and  tubercle  bacilli, 
and  in  the  diseases  of  the  intestinal  canal  occasioned  by  those  bac- 
teria the  follicles  and  Peyer's  patches  are  the  seat  of  the  earliest 
and  most  extensive  ulcerations.  The  tonsils,  which  have  the  same 
igeneral  structure,  are  still  more  prone  to  infection  of  various  kinds, 


144 


NORMAL  HISTOLOGY. 


for  they  are  more  directly  exposed  to  the  action  of  bacteria  that  may 
gain  access  to  the  mouth. 

The  reason  for  this  vulnerability  appears  to  lie  in  the  close  prox- 
imity of  the  lymphatics  to  the  surface  and  their  meagre  protection 
by  a  thin  layer  of  epithelium  liable  to  abrasion  or  destruction.  The 
solitary  follicles  of  the  intestine,  for  example,  are  covered  with  a 
single  layer  of  columnar  epithelium  (Fig.  121). 

The  lymphadenoid  tissue  of  the  tonsil,  it  is  true,  is  protected  by 
a  layer  of  stratified  epithelium ;  but  the  surface  of  the  tonsil  is  invag- 
inated  to  form  the  crypts  of  that  organ,  and  within  those  crypts  it 

FIG.  123. 


Section  through  one  of  the  crypts  of  the  tonsil.  (Stohr.)  e,  stratified  epithelium  of  the  gen- 
eral surface,  continued  into  the  crypt;  /,  follicles  containing  germinal  foci.  Between 
the  follicles  is  a  more  diffusely  arranged  lymphadenoid  tissue,  s,  material  within  the 
crypt,  composed  in  part  of  lymphoid  corpuscles  that  have  wandered  through  the  strati- 
fied epithelium. 

is  possible  for  bacteria  to  multiply  and  produce  such  an  accumula- 
tion of  poisonous  products  as  to  destroy  the  integrity  of  the  epithe- 
lium and  so  permit  an  invasion  of  the  lymphadenoid  tissue  beneath. 
We  therefore  find  the  tonsils  specially  prone  to  such  inflammatory 


THE  DIGESTIVE  ORGANS. 


FIG.  124. 


145 


Section  through  the  fundus  of  a  crypt.  (Benda  and  Guenther's  Atlas.)  a,  stratified  epithe- 
lium, desquamating  at  its  surface ;  6,  deep  portion  of  the  lymphadenoid  tissue,  in  which 
proliferation  of  lymphoid  cells  takes  place  as  well  as  in  the  follicles  represented  in  Fig.  123. 

processes  as  tonsillitis  and  diphtheritic  inflammation  (Figs.  123  and 
124). 

10 


CHAPTER  XI. 
THE  LIVER. 

THAT  portion  of  the  liver  which  is  exposed  in  the  abdominal 
cavity  is  covered  by  a  reflection  of  the  peritoneum,  closely  attached 
to  the  organ,  because  its  deeper  side  is  continuous  with  the  fibrous 
structures  or  interstitial  tissue  of  the  liver  itself.  This  serous  cover- 
ing is  so  thin  that  the  substance  of  the  liver  can  be  readily  seen 
through  it. 

At  the  portal  fissure,  the  serous  coat  having  been  reflected  from 
it,  the  liver  is  covered  with  a  loose  areolar  tissue  in  which  the  main 
trunks  of  all  but  one  of  the  vessels  connected  with  it  are  situated : 
namely,  the  por_tal__yein,  hepatic  artery,  gall-duct,  and  lymjDhatics. 
These  vessels  enter  the  liver  together  at  this  place,  and  are  closely 
associated  with  each  other  in  all  their  ramifications,  being  supported 
throughout  by  areolar  tissue,  which  is  continuous  with  that  at  the 
portal  fissure  and  with  the  interstitial  tissue  of  the  liver. 

These  vessels,  with  their  supporting  fibrous  investment,  called 
Olisson's  capsule,  ramify  in  the  liver  in  such  a  way  as  to  resemble 
a  tree  with  a  multitude  of  branches  and  twigs,  each  composed  of 
divisions  of  all  the  vessels  named. 

The  hepa±La,X£Ln_enters  the  liver  at  a  different  place,  and  also 
suffers  a  tree-like  subdivision ;  but  its  branches  are  surrounded  by  a 
very  much  smaller  amount  of  fibrous  tissue,  which  may  be  regarded 
as  but  a  slightly  reinforced  portion  of  the  interstitial  tissue  of  the 
organ. 

Sections  of  the  liver  (Fig.  125)  will  reveal  portions  of  these  two 
trees,  cut  in  various  directions  with  respect  to  their  axes.  It  will 
be  observed  that  the  twigs  and  larger  branches  of  the  trees  are 
nowhere  in  close  relations  to  each  other,  showing  that  the  hepatic 
vein,  in  all  its  ramifications,  is  separated  from  the  other  vessels  by 
the  parenchyma  of  the  organ.  If  we  select  some  part  of  a  section 
which  contains  one  of  the  smallest  branches  of  the  hepatic  vein,  and 
cut  across  its  axis  so  that  its  lumen  appears  round,  we  shall  notice 
that  at  about  equal  distances  from  it  there  are  sections  of  two, 

146 


THE  LIVER.  147 

three,  or  four  twigs  of  the  compound  tree.  In  these  the  gall-duct 
can  be  identified  by  its  distinct  lining  of  columnar  or  cubical  epi- 
thelium, and  the  hepatic  artery  distinguished  from  the  portal  vein 
by  its  relatively  thick  wall  as  compared  with  the  size  of  its  lumen. 
These  vessels  are  collectively  known  as  the  interlobular  vessels. 
Between  and  around  them  is  the  areolar  fibrous  tissue,  which  forms 
a  part  of  Glisson's  capsule,  and  which  is  abundantly  supplied  with 

FIG.  125. 


Diagrammatic  sketch  of  a  section  of  liver :  a,  central  vein  (radicle  of  the  hepatic  vein) ;  6,  b, 
branches  of  the  portal  vein ;  c,  c,  branches  of  the  hepatic  artery  ;  d,  d,  small  bile-ducts  ; 
e,  lymphatic  vessel ;  b,  c,  d,  e  are  enclosed  in  areolar  tissue,  which  is  continuous  with 
Glisson's  capsule ;  /,  liver-cells ;  g,  line  indicating  the  junction  and  blending]  of  two 
neighboring  lobules. 


lymphatic  spaces  and  vessels  in  the  fibrous  tissue.  The  lymphatics 
appear  as  clear  spaces  with  smooth  walls,  some  of  them  with  dis- 
tinct endothelial  linings,  but  almost  devoid  of  any  other  wall. 

The  parenchyma  may  be  subdivided  into  portions  which  surround 
the  smallest  branches  of  the  hepatic  vein,  and  are  bounded  by 
imaginary  lines  connecting  the  groups  of  interlobular  vessels. 
These  subdivisions  are  called  "lobules"  of  the  liver.  In  the 
human  liver  they  blend  at  their  peripheries,  between  the  masses  of 
connective  tissue  enclosing  the  interlobular  vessel ;  but  in  the  liver 
of  the  pig  these  lobules  are  veritable  subdivisions  of  the  liver,  and 


148 


NORMAL  HISTOLOGY. 


are  separated  by  septa  of  fibrous  tissue,  the  interlobular  vessels 
lying  in  the  lines  formed  by  the  junction  of  three  such  septa. 

Connecting  the  branches  of  the  portal  vein  with  the  hepatic  vein 
is  a  plexus  of  capillaries,  called  the  intralobular  vessels,  through 
which  the  blood  passes  from  the  portal  vessels  to  the  radicles  of  the 
hepatic  vein  and  thence  into  the  general  circulation.  These  intra- 
lobular vessels  also  receive  blood  from  the  hepatic  artery,  the 
capillaries  from  which  join  them  at  a  little  distance  from  the 
periphery  of  the  lobule.  The  radicles  of  the  hepatic  vein  are 
called  the  central  veins,  from  their  situation  in  the  axes  of  the 
lobules,  which  are  conceived  as  having  a  somewhat  cylindrical 
shape  (Fig.  126). 

FIG.  126. 


Vessels  and  bile-ducts  of  a  lobule  of  a  rabbit's  liver  in  transverse  section.  (Cadiat.)  a,  cen- 
tral vein  ;  b,  b,  interlobular  veins  (branches  of  the  portal  vein) ;  c,  interlobular  bile-duct, 
receiving  capillary  bile-ducts  from  the  lobule.  Between  a  and  b  is  the  capillary  plexus 
called  the  intralobular  vessels.  The  biliary  radicles  are  not  represented  throughout  the 
figure,  and  the  branches  of  the  hepatic  artery  have  been  wholly  omitted. 

Between  the  interlobular  capillaries  are  rows  of  epithelial  cells, 
which  constitute  the  functional  part  of  the  liver,  its  parenchyma. 
They  appear  to  touch  the  walls  of  the  capillaries,  but  are,  in  reality, 
separated  from  them  by  a  narrow  lymph-space  (Fig.  127).  In  the 


THE  LIVER. 


149 


human  liver  the  epithelial  cells  of  the  parenchyma  form  a  plexus 
lying  in  the  meshes  of  the  capillary  network  of  the  interlobular 
vessels. 

It  requires  an  eifort  of  the  imagination  to  conceive  of  a  third  plexus 
within  the  lobule,  but  such  a  plexus  exists,  being  formed  of  the 
radicles  of  the  gall-duct.  These  are  minute  channels  situated 
between  contiguous  epithelial  cells,  each  of  which  is  grooved  upon 
its  surface  to  form  half  of  the  tiny  canal.  The  cells  themselves 
have  fine  channels  running  from  the  bile-capillaries  into  their  cyto- 
plasm and  ending  there  in  little  rounded  expansions.  It  is  difficult 
to  detect  these  bile-capillaries  in  ordinary  sections  of  the  liver, 
unless  they  have  been  previously  injected  through  the  main  duct ; 
but  with  a  high  power  their  cross-sections  may  sometimes  be  clearly 
seen,  appearing  as  little  round  or  oval  spaces  at  the  junction  of  two 


FIG.  127 


FIG.  128. 


Fig.  127.— Perivascular  lymphatic  of  the  human  liver.  (Disse.)  c,  capillary  in  longitudinal 
section ;  a,  lymphatic  space  between  the  capillary  and  row  of  epithelial  cells ;  b,  wall 
of  the  lymphatic  space,  slightly  separated  from  the  liver-cells  and  drawn  a  little  em- 
phatically; I,  liver-cells;  d,  bile-capillaries  in  cross-section,  with  their  intracellular 
ramifications. 

Fig.  128.— Bile-capillaries  between  the  liver-cells,  with  minute  channels  penetrating  the  cells 
and  communicating  with  secretory  vacuoles  within  the  cytoplasm.  Injected  liver  of  the 
rabbit.  (Pfeiffer.) 


epithelial  cells,  midway  between  the  nearest  capillary  bloodvessels. 
Throughout  their  Avhole  course  they  appear  to  be  separated  from 
the  nearest  bloodvessels  by  a  distance  approximately  equal  to  half 
the  diameter  of  one  of  the  epithelial  cells.  It  is  this  fact  that  makes 
it  so  difficult  to  frame  a  mental  picture  of  their  distribution  in  the 
lobule  (Fig.  128). 

The  nerves  supplying  the  liver  ramify  in  extremely  delicate,  non- 


150 


NORMAL  HISTOLOGY. 


medullated  fibrils,  which  ramify  throughout  the   substance  of  the 
liver  and  terminate  in  minute  twigs  among  its  epithelial  cells. 

The  epithelial  cells  of  the  liver  have  a  cubical  shape,  the  grooved 
and  other  surfaces  that  come  in  contact  with  neighboring  cells  being 
flat,  while  the  remaining  surfaces  may  be  somewhat  rounded.  The 
cytoplasm  is  granular,  and,  except  after  a  considerable  period  of 
starvation,  more  or  less  abundantly  infiltrated  with  irregular  gran- 
ules and  masses  of  glycogen  and  globules  of  fat  (Fig.  129).  The 

FIG.  129. 


Portion  of  hepatic  lobule  of  the  rabbit ;  cells  infiltrated  with  glycogen.  (Barfurth.)  The 
animal  had  been  fed  for  twenty-four  hours  on  wheat-bread,  to  promote  the  storage  of  gly- 
cogen within  the  liver-cells.  The  cells  in  close  proximity  to  the  central  vein  contain 
the  largest  amount  of  glycogen,  which  appears  to  fill  the  cytoplasm.  Further  from  the 
central  vein  the  cells  contain  less  glycogen,  which  is  most  abundant  in  that  portion  of 
the  cell  turned  toward  the  centre  of  the  lobule.  Fat-globules  are  most  abundant  in  the 
cells  at  the  periphery  of  the  lobule.  No  fat-globules  are  represented  in  this  figure. 

glycogen  dissolves  out  of  the  cells  during  the  ordinary  processes  of 
fixation  and  hardening  preparatory  to  the  preparation  of  sections, 
leaving  spaces  in  the  cytoplasm,  which  cause  it  to  have  a  coarsely 
reticulated  appearance  in  cases  where  the  glycogen  was  abundant. 
This  reticulation  would  render  it  impossible  to  distinguish  the 
minute  intracellular  bile-passages.  Each  cell  has  a  round  vesicular 
nucleus  near  its  centre.  In  rare  instances  two  nuclei  may  be  found 
in  a  single  cell. 

It  will,  perhaps,  make  the  structure  of  the  liver  a  little  more 
comprehensible  if  it  is  stated  that  the  liver  of  some  of  the  lower 
animals  is  a  tubular  gland,  the  tubes  of  which  are  lined  with  a  layer 


THE  LIVER.  151 

of  epithelium.  In  the  human  liver  this  tubular  structure  is  dis- 
guised by  the  facts  that  the  tubules  anastomose  with  each  other,  and 
that  their  lumina  are  very  minute  and  bounded  by  only  two  cells 
when  seen  in  cross-section.  So  inconspicuous  are  these  lumina  that 
a  casual  glance  at  a  section  of  a  liver  would  not  reveal  the  fact  that 
it  was  a  glandular  organ. 

The  interstitial  tissue  of  the  liver  consists  of  a  few  sparsely 
distributed  fibres  continuous  with  those  of  Glisson's  capsule. 

The  intricate  structure  of  the  liver  prepares  us  for  the  fact  that 
its  function  is  an  extremely  complex  one.  It  is  a  secreting  gland, 
elaborating  the  bile  and  discharging  it  into  the  duodenum.  But 
the  bile  has  more  than  one  purpose.  It  aids  in  the  digestion  and 
absorption  of  food,  and  it  also  contains  excrementitious  matters 
destined  to  leave  the  body  through  the  alimentary  tract.  Even  the 
secretory  function  of  the  liver,  therefore,  serves  a  double  purpose : 
the  supply  of  substances  useful  to  the  organism  and  the  elimina- 
tion of  products  that  would  be  detrimental  if  retained. 

But  the  function  of  the  liver  is  not  confined  to  the  elaboration 
of  the  bile.  It  also  acts  as  a  reservoir  for  the  storage  of  nourish- 
ment, which  can  be  drawn  upon  as  needed  by  the  organism.  This 
is  the  meaning  of  the  glycogen  and  fat  which  have  infiltrated  the 
cells. 

The  food-materials  that  are  absorbed  from  the  digestive  tract  pass 
into  the  system  through  two  channels :  the  lymphatic  and  the  portal 
circulations.  The  latter  carries  them  to  the  liver,  where  some  of 
the  fat,  probably  after  desaponification,  is  taken  up  by  the  epithelial 
cells,  which  also  appropriate  a  portion  of  the  sugar  in  the  portal 
blood,  transforming  it  into  glycogen  and  holding  it  in  that  form 
until  a  relative  deficiency  of  glucose  in  the  blood  reveals  its  need 
by  the  system. 

The  blood  comes  into  such  close  relations  with  the  epithelial  cells 
of  the  liver  that  an  interchange  of  soluble  substances  between  them 
appears  to  be  about  as  easy  a  matter  as  the  interchange  of  gases 
between  the  blood  and  the  air  in  the  lungs ;  and,  as  in  the  latter 
case,  this  interchange  is  mutual :  some  matter  passing  from  the 
blood  to  the  liver-cells  and  some  from  the  cells  to  the  blood.  In 
the  lung  there  is  a  gaseous  regeneration  of  the  blood ;  in  the  liver, 
a  renovation  as  to  certain  of  its  soluble  constituents. 

The  Gall-bladder. — The  bile  is  secreted  continuously  by  the  liver, 
for  it  is  an  excrement ;  but  it  is  discharged  intermittently  into  the 


152  NORMAL  HISTOLOGY. 

alimentary  tract,  as  required  by   the  digestive  processes.      In  the 
interval  it  is  stored  in  the  gall-bladder. 

The  gall-bladder  is  lined  with  columnar  epithelium,  capable  of 
secreting  mucus.  Beneath  this  is  a  layer  of  fibrous  tissue,  which 
becomes  areolar  and  supports  the  chief  bloodvessels  and  lymphatics. 
Beneath  this  is  the  wall  of  the  organ,  composed  of  interlacing 
bands  of  fibrous  and  smooth  muscular  tissues.  The  surface  is 
invested  by  a  portion  of  the  peritoneum.  The  excretory  bile-duct 
has  a  similar  structure. 


CHAPTER  XII. 

THE  URINARY  ORGANS. 

THE  urine  is  secreted  by  the  kidney,  whence  it  passes  succes- 
sively through  the  renal  pelvis,  ureter,  bladder,  and  urethra  into 
the  outer  world. 

1.  The  kidney  is  made  up  of  homologous  parts  or  lobes,  which 
are  readily  distinguished  in  early  life  by  the  superficial  furrows 
marking  their  lines  of  junction.  In  later  years  these  depressions 
on  the  surface  of  the  kidney  disappear.  Each  of  the  lobes  corre- 
sponds to  one  of  the  papillae  of  the  kidney  and  the  pelvic  calix  that 
embraces  it.  In  some  of  the  lower  animals — e.  g.y  the  rabbit — the 
kidney  has  but  one  papilla,  so  that  the  whole  renal  pelvis  in  those 
animals  corresponds  to  a  single  calix  in  man. 

The  kidney  is  a  compound  tubular  gland  of  peculiar  construc- 
tion, the  tubules  taking  origin  from  little  spherical  bodies,  called 
Malpighian  bodies,  instead  of  from  simple  blind  extremities,  and, 
after  running  a  definite  and  somewhat  complicated  course,  uniting 
successively  with  several  others  to  form  the  excretory  ducts,  called 
the  "  collecting  tubules,"  which  open  into  the  calices  near  the  tips 
of  the  papillae. 

If  a  section  of  the  organ  be  made  through  its  convexity  down  to 
the  pelvis,  the  papillae  will  be  seen  projecting  into  the  calices  of  the 
pelvis,  and  it  will  be  noticed  that  each  papilla  forms  the  apex  of  a 
pyramidal  portion  of  tissue  having  a  different  tint  and  texture  from 
the  rest  of  the  kidney.  These  pyramids  form  the  "medulla"  of 
the  organ  (Fig.  130). 

The  bloodvessels  supplying  nearly  all  its  substance  enter  the 
kidney  near  the  bases  of  the  pyramids,  having  approached  the 
organ  through  the  fat  that  lies  around  the  calices.  Within  the 
kidney  they  break  up  into  branches  that  run  along  the  base  of  each 
pyramid  in  that  portion  of  the  organ  which  is  called  the  "  boundary 
zone."  Between  that  zone  and  the  convex  surface  of  the  kidney 
the  tissue  is  known  as  the  "cortex." 

The  arrangement  of  the  renal  tubules,  which  make  up  the  chief 

153 


154 


NORMAL  HISTOLOGY. 


bulk   of  the  kidney,  can  be  most  easily  understood  if  they  are 
traced  back  from  their  openings  at  the  apex  of  the  pyramid  to  their 


FIG.  130. 


Lobule 


Diagrammatic  sketch  of  a  section  of  the  kidney:  a,  columnar  epithelium  covering  the 
external  surface  of  the  pyramid  and  continuous  on  the  one  hand  with  the  columnar 
epithelium  lining  the  collecting  tubules  within  the  pyramid,  and  on  the  other  hand  with 
the  transitional  epithelium  lining  the  calices  and  renal  pelvis.  This  transitional  epi- 
thelium is  indicated  at  b.  It  rests  upon  the  fibrous  tissue  of  the  calices  and  pelvis,  which 
becomes  continuous  with  the  fibrous  capsule  of  the  kidney  at  the  junction  of  the  calices 
with  that  organ.  Outside  of  this  capsule  is  the  perinephric  fat,  indicated  in  the  figure 
between  the  calices.  The  vessels  approach  the  kidney  through  this  fat,  entering  its  sub- 
stance near  the  bases  of  the  pyramids  and  forming  the  vascular  arcades  (e,  arterial  arcade). 
From  these  arcades  the  interlobular  vessels  proceed,  between  the  medullary  rays  and  in 
the  labyrinth,  toward  the  convex  surface  of  the  kidney,  d,  interlobular  artery,  giving 
off  branches,  the  afferent  vessels,  to  the  MfJpighian  bodies.  The  extensions  of  the  cor- 
tical substance  between  tbe  pyramids,  c,  fire  known  as  the  columns  of  Bertini.  During 
infancy  the  lobes  of  the  kidney  are  marked  by  sulci  upon  the  surface  of  the  organ.  With 
the  growth  of  the  organ  these  lobes  blend  with  each  other,  and  the  sulci  between  them 
become  indistinct  or  are  wholly  obliterated.  The  columns  of  Bertini  are  made  up  of  the 
blended  lateral  portions  of  the  cortex  of  two  contiguous  lobes. 

origins  in  the  Malpighian  bodies.  The  different  portions  of  the 
tubules  present  somewhat  different  characters,  and  have  received 
special  names. 


THE   URINARY  ORGANS.  155 

The  collecting  tubes,  which  open  into  the  calix  at  the  apex  of  the 
pyramid,  are  straight,  and  lie  nearly  parallel  to  each  other  and  to 
the  axis  of  the  pyramid,  and,  therefore,  nearly  perpendicular  to  the 
base  of  the  pyramid.  As  they  are  followed  from  the  apex,  in  a 
direction  the  reverse  of  that  taken  by  the  urine  in  flowing  through 
them,  they  branch  dichotomously,  and  the  branches  become  pro- 
gressively smaller.  At  the  base  of  the  pyramid  these  straight 
tubules  are  collected  into  bundles  that  radiate  toward  the  convex 
surface  of  the  kidney,  and  are  called  the  "  medullary  rays."  In 
these,  and  in  the  part  of  the  pyramid  that  is  near  the  boundary- 
zone,  the  collecting  tubes  are  associated  with  other  straight  portions 
of  the  tubules,  "  Henle's  tubes,"  which  will  be  described  pres- 
ently. From  the  medullary  rays  the  tubules  pass  into  the  region 
between  those  rays  in  the  cortical  portion  of  the  kidney.  This 
region  of  the  cortex  is  known  as  the  "  labyrinth."  Here  the  tub- 
ules lose  their  straight  character  and  become  much  contorted,  form- 
ing the  "second  convoluted  tubules."  They  then  re-enter  the 
medullary  rays,  which  they  descend  for  a  variable  distance  into  the 
pyramid,  constituting  the  "  ascending  branches  of  Henle's  tubes," 
which  make  a  sharp  turn,  "  Henle's  loop,"  and  then  retrace  their 
course  up  the  medullary  rays  into  the  cortical  portion  of  the  kidney, 
"descending  branches  of  Henle's  tube."  They  then  pass  again 
into  the  labyrinth  and  form  the  "  first  convoluted  tubules,"  which 
finally  merge  into  the  structure  of  the  Malpighian  bodies,  also 
situated  in  the  labyrinth.  In  consequence  of  the  passage  of  tubules 
from  them  into  the  surrounding  labyrinth  the  medullary  rays  become 
smaller  as  they  are  followed  from  the  base  of  the  pyramid,  and 
eventually  disappear  before  the  capsule  of  the  kidney  is  reached. 
They  are  completely  surrounded  by  the  labyrinth. 

If  we  now  follow  the  course  of  the  urine  in  its  way  from  the 
Malpighian  body  to  the  outlet  of  the  tubule,  we  shall  find  that  it 
passes  through  the  following  divisions  of  the  tubule  :  1,  the  "first 
convoluted  tubule ; "  2,  the  "  descending  branch  of  Henle's  tube ; " 
3,  "  Henle's  loop ; "  4,  the  "  ascending  branch  of  Henle's  tube ; " 
5,  the  "  second  convoluted  tubule  ; "  6,  the  "  collecting  tube."  Of 
these,  the  two  convoluted  tubules  are  situated  in  the  labyrinth  ;  all 
the  rest  in  the  medullary  rays  and  pyramid.  All  of  the  portions, 
with  the  exception  of  the  convoluted  tubules  and  the  loop,  are 
straight  and  lie  parallel  to  each  other  (Fig.  131). 

Before  entering  more  particularly  into  the  structure  of  the  renal 


156 


NORMAL  HISTOLOGY. 
FIG.  131. 


Diagram  showing  the  course  of  the  renal  tubules  within  the  kidney.  (Klein.)  A,  cortex  :  a, 
subcapsuiar  portion  destitute  of  Malpighian  bodies ;  a',  inner  portion,  also  devoid  of  Mal- 
pighian  bodies.  B,  boundary.  C,  portion  of  the  medulla  at  the  base  of  the  pyramid. 
1,  Bowman's  capsule  surrounding  the  glomerulus  ;  2,  neck  of  the  capsule  and  beginning 
of  the  uriniferous  tubule;  3,  first  convoluted  tubule;  4,  spiral  portion  of  the  first  con- 
voluted tubule  in  the  medullary  ray ;  5,  descending  limb  of  Henle's  tube ;  6,  Henle's 
loop ;  7,  8,  9,  ascending  limb  of  Henle's  tube ;  10,  irregular  transition  to  the  second  con- 
voluted tubule;  11,  second  convoluted  tubule;  12,  transition  from  second  convoluted 
tubule  to  the  collecting  tubule ;  13, 14,  collecting  tubule,  joined  below  by  others  to  form 
the  excretory  duct,  which  opens  at  the  apex  of  the  pyramid. 

tubule,  it  will  be  best  to  complete  this  general  sketch  by  considering 
the  course  of  the  bloodvessels. 

As  has  already  been  said,  the  vessels  enter  the  kidney  between 
the  calices  and  pyramids  and  are  distributed  in  branches  that  lie 


THE   URINARY  ORGANS. 


157 


FIG.  132. 


parallel  to  the  bases  of  the  latter,  and,  therefore,  to  the  convex 
surface  of  the  organ,  and  are  situated  in  the  boundary-zone.  The 
arterial  branches  in  this  location  form  the 
"arterial  arcade."  From  this  arcade  per- 
pendicular branches,  the  "  interlobular  arte- 
ries," pass  toward  the  capsule,  taking  a 
straight  course  through  the  labyrinth  be- 
tween the  medullary  rays.  In  this  course 
they  give  off  branches,  the  "afferent  ves- 
sels," which  go  to  the  Malpighian  bodies. 

FIG.  133. 


FIG.  132.— Diagram  showing  the  course  of  the  bloodvessels  within  the  kidney.  (Ludwlg.)  a, 
interlobular  artery ;  6,  interlobular  vein ;  c,  Malpighian  body,  with  the  afferent  vessel 
entering  it  from  the  interlobular  artery,  and  the  efferent  vessel  leaving  it  to  take  part  in 
the  formation  of  the  capillary  plexus  between  the  renal  tubules;  rf,  vena  stellata;  e, 
arterisc  rectse ;  /,  venae  rectse ;  g,  capillary  plexus  around  the  mouths  of  the  excretory 
ducts. 

FIG.  133.— Injected  glomerulus  from  the  horse.  (Kolliker,  after  Bowman.)  a,  interlobular 
artery ;  of,  afferent  vessel ;  m,  m,  capillary  loops  forming  the  glomerulus ;  tf,  efferent 
vessel ;  b,  capillary  network  in  the  labyrinth  and  medullary  rays. 

The  main  artery  becomes  smaller  in  giving  off  these  branches,  and 
finally  ends  in  terminal  afferent  vessels  (Fig.  132). 


158 


NORMAL  HISTOLOGY. 


Within  the  Malpighian  body  the  afferent  vessel  divides  abruptly 
into  a  number  of  capillary  loops,  which  are  compacted  together  to 
form  a  globular  mass,  called  the  "  glomerulus  "  (Fig.  133).  These 
loops  rejoin  to  form  the  "efferent"  vessel,  which  is  somewhat 
smaller  than  the  afferent  vessel,  and  leaves  the  Malpighian  body 
at  a  point  close  to  that  at  which  the  afferent  vessel  enters  it. 

FIG.  134. 


Sketch  of  a  Malpighian  body  from  kidney  of  a  rabbit :  a,  interlobular  artery ;  6,  afferent 
vessel ;  c,  capillary  springing  from  afferent  vessel ;  d,  Bowman's  capsule,  with  epithelial 
lining  reflected  upon  the  surface  of  the  glomerulus  ;  e,  cavity  of  the  capsule  into  which 
the  watery  constituents  of  the  urine  are  first  discharged;  /,  beginning  of  a  uriniferous 
tubule ;  g,  convoluted  tubules  of  the  labyrinth.  Between  these  tubules  and  the  capsule 
are  capillary  bloodvessels  derived  from  the  efferent  vessel  (which  is  not  shown,  but 
emerges  from  the  capsule  near  the  afferent  vessel,  on  a  different  level  from  that  repre- 
sented). These  and  other  structures  are  held  in  place  by  an  areolar  tissue,  containing 
lymphatic  spaces,  some  of  which  are  represented. 

Soon  after  leaving  the  Malpighian  body  the  efferent  vessel  breaks 
up  into  a  second  set  of  capillaries,  which  lie  among  the  convoluted 
tubules  of  the  labyrinth  and  also  penetrate  into  the  medullary  rays, 
to  be  distributed  between  the  tubules  composing  them.  This  capil- 
lary network  extends  also  into  the  pyramid,  in  which  the  capilla- 


THE   VRINARY  ORGANS. 


159 


ries  run,  for  the  most  part,  parallel  to  the  renal  tubules,  with  com- 
paratively few  transverse  anastomosing  branches.  For  this  reason 
they  have  been  called  the  "vasa  recta."  They  also  receive  blood 
from  little  twigs  given  off  from  the  arterial  arcade. 

The  blood  from  the  intertubular  capillaries  is  collected  in  veins, 
which  run  a  course  parallel  to  that  of  the  arteries  and  lie  in  close 
proximity  to  them.  They  have  received  names  similar  to  those  of 
the  corresponding  arteries :  "  interlobular  veins,"  "  venae  rectee," 
and  "  venous  arcade."  Relatively  large  veins  also  leave  the  kidney 
from  beneath  the  capsule  on  the  convex  surface  of  the  organ.  They 
are  called  the  "  stellate  veins." 

The  Malpighian  body  is  enclosed  by  a  thin  fibrous  capsule 
(Bowman's  capsule),  which  is  perforated  at  two  opposite  points  to 
permit  the  passage  on  the  one  hand  of  the  afferent  and  efferent 
vessels,  and  on  the  other  hand  to  allow  of  a  communication  between 
its  cavity  and  the  beginning  of  the  uriniferous  tubule.  When  dis- 
tended with  blood  the  glomerulus  nearly  fills  this  capsule,  but  when 
collapsed  it  is  retracted  toward  the  attachment  formed  by  the  ves- 
sels that  pierce  the  capsule.  It  is  covered  by  a  single  layer  of  epi- 


FIG.  135. 


FIG.  136. 


Cross-sections  of  convoluted  tubules  lined  with  cells  in  different  states  of  activity.  (Disse.) 
Fig.  135.— From  a  criminal  directly  after  execution.  Cells  in  a  state  of  rest.  The  cells  are 

low  and  granular,  and  present  a  striation  of  their  free  ends  resembling  cilia. 
Fig.  136.— From  a  cat.  The  cells  are  enlarged,  because  charged  with  material  to  be  excreted, 
and  the  striated  border  is  nearly  obliterated.  Similar  appearances  have  been  observed 
in  the  human  kidney.  In  one  of  the  lower  cells  in  this  figure  a  faint  striation  of  the 
attached  end  is  just  discernible.  This  increases  in  distinctness  as  the  cell  becomes  sur- 
charged with  excretory  material,  when  the  more  central  portion  of  the  cytoplasm 
becomes  hyaline  and  contains  the  nucleus. 

thelial  cells,  which  is  reflected  at  that  attachment  and  forms  a  lining 
for  the  inner  surface  of  the  capsule  to  the  point  where  its  cavity 
opens  into  the  lumen  of  the  renal  tubule.  Here  the  epithelial  lining 
becomes  continuous  with  that  of  the  tubule  (Fig.  134). 

The  different  portions  of  the  uriniferous  tubule  differ  in  their 


160  NORMAL  HISTOLOGY. 

external  diameters,  the  diameters  of  their  lumina,  and  the  character 
of  their  epithelial  linings.  The  appearance  of  the  epithelial  cells 
differs,  however,  in  accordance  with  their  state  of  functional  activity 
(Figs.  135  and  136). 

The  first  convoluted  tubule  is  relatively  large,  and  is  lined  with 
large  epithelial  cells,  which  project  into  the  tubule  about  one-third 
of  its  diameter.  The  cells  have  round  nuclei  situated  near  their 
centres,  and  are  granular,  with  an  appearance  of  radiate  striation 
in  their  deeper  halves  when  charged  with  secretion. 

The  descending  branch  of  Henle's  tube  has  a  smaller  diameter, 
but  its  lumen  is  wide  in  consequence  of  the  thinness  of  the  clear 
epithelial  cells  lining  it.  In  the  ascending  branch  the  lumen  is 
again  smaller,  although  the  diameter  of  the  tube  is  larger,  because 
the  lining  cells  are  thicker,  somewhat  resembling  those  of  the  first 
convoluted  tubule.  The  transition  from  the  character  of  the  de- 
scending to  that  of  the  ascending  branch  does  not  always  take  place 
exactly  at  the  loop. 

The  second  convoluted  tubule  is  a  little  smaller  than  the  first,  and 
is  lined  with  cells  that  are  not  quite  so  granular  and  a  little  more 
highly  refracting. 

The  collecting  tubules  are  lined  with  columnar  epithelium,  the 
cells  of  which  become  longer  as  the  diameter  of  the  tube  increases 
in  its  progress  toward  the  apex  of  the  pyramid. 

The  epithelial  lining  throughout  the  course  of  the  renal  tubule 
is  said  to  rest  upon  a  thin,  homogeneous  basement-membrane  inter- 
posed between  it  and  the  interstitial  fibrous  tissue.  The  latter  is 
present  in  small  amount,  and  partakes  of  the  character  of  an  areolar 
tissue,  holding  the  tubules  and  bloodvessels  in  place.  It  is  rather 
abundantly  supplied  with  lymphatics. 

For  the  study  of  the  uriniferous  tubules  sections  made  trans- 
verse to  the  course  of  the  straight  tubules  will  be  found  very  use- 
ful. In  the  cortex  the  medullary  rays,  with  their  descending  and 
ascending  branches  of  Henle's  tubes  and  their  collecting  tubules, 
will  appear  surrounded  by  the  labyrinth,  made  up  of  the  con- 
voluted tubules,  Malpighian  bodies,  and  larger  vessels,  the  latter  in 
cross-section.  Near  the  apex  of  the  pyramid  cross-sections  of  the 
larger  collecting  tubes  and  of  the  vasa  recta  will  be  seen ;  and  near 
its  base  the  smaller  collecting  tubes  and  the  tw7o  limbs  of  Henle's 
tube,  with,  possibly,  here  and  there  a  "  loop  "  in  nearly  longitudinal 
section,  will  appear.  Among  all  these  sections  of  the  tubules  the 


THE   URINARY  ORGANS. 


161 


interstitial  tissue  with  its  capillaries  and  lymphatics  will  complete 
the  picture  (Figs.  137  and  138). 


FIG.  138. 


Sections  from  a  rabbit's  kidney,  made  perpendicular  to  the  course  of  the  straight  tubules. 

Fig.  137.— Through  a  portion  of  the  pyramid  :  a,  lower  portions  of  the  collecting  tubules 
(excretory  ducts) ;  6,  Henle's  loop  in  tangential  section ;  c,  capillary  bloodvessels ;  d, 
lymphatic  ;  e,  descending  limb  of  Henle's  tube. 

Fig.  138.— Through  part  of  a  medullary  ray  and  the  adjoining  labyrinth  :  a,  a,  a,  a,  convoluted 
tubules  in  the  labyrinth ;  6,  spiral  tubule ;  c,  descending  limb  of  Henle's  tube  ;  d,  ascend- 
ing limb  of  Henle's  tube :  e,  irregular  tubule ;  /,  collecting  tubule ;  g,  capillary  blood- 
vessel. 


The  nerves  of  the  kidney  are  small  and  apparently  not  abundant. 
Their  larger  branches  follow  the  courses  of  the  arteries. 
11 


162  NORMAL  HISTOLOGY. 

The  external  surface  of  the  kidney  is  covered  with  a  capsule  of 
fibrous  tissue,  which  on  its  deeper  surface  becomes  continuous  with 
the  interstitial  tissue,  so  that  its  vascular  supply  communicates  with 
the  capillaries  in  the  superficial  portions  of  the  kidney. 

The  fibrous  capsule  of  the  kidney  becomes  continuous  at  the 
hilum  of  that  organ  with  the  fibrous  coats  of  the  calices  and  pelvis, 
and,  through  these,  with  those  of  the  ureter  and  bladder. 

The  columnar  epithelium  lining  the  collecting  tubes  is  continuous 
with  a  layer  of  similar  cells  covering  the  papillae. 

The  watery  constituent  of  the  urine  is  secreted  in  the  Malpighian 
body,  where  it  passes  from  the  blood  through  the  capillary  walls  of 
the  glomerulus  into  the  cavity  of  Bowman's  capsule.  Under  nor- 
mal conditions  it  is  free  from  albumin,  and,  therefore,  is  unlike  the 
serum  that  passes  through  the  walls  of  the  capillaries  in  other  parts 
of  the  body.  It  has  been  thought  that  this  difference  was  attrib- 

FIG.  139. 


KEr 


Capillary  loop  from  the  glomerulus  of  the  frog.  (Nussbaum.)  Ez,  endothelial  wall  of  the 
capillary  bloodvessel;  Ek,  nucleus  of  one  of  the  endothelial  cells  (only  three  such 
nuclei  are  shown  in  the  figure) ;  KE,  nucleus  of  one  of  the  epithelial  cells  investing  the 
capillary.  The  boundaries  of  these  cells  are  not  reproduced  in  the  figure.  At  the  left 
of  the  cut  three  epithelial  cells  have  been  partially  reflected  away  from  the  capillary 
wall. 

utable  to  the  functional  action  of  the  endothelium  in  the  glomerulus, 
though  morphologically  it  is  similar  to  that  throughout  the  body. 
It  is  more  probable  that  the  epithelium  covering  the  glomerulus  has 


THE   URINARY  ORGANS. 


163 


something  to  do  with  the  prevention  of  a  loss  of  albumin  (Fig.  139). 
In  disease  of  the  kidney,  alterations  in  the  glomerulus  and,  per- 
haps, in  other  parts  of  the  kidney  permit  albumin  to  pass  into  the 
secretion. 

The  epithelium  lining  the  uriniferous  tubules  discharges  its 
secretion  into  the  lumen  of  the  tubules,  whence  it  is  carried  by 
the  stream  flowing  from  the  Malpighian  bodies.  The  epithelial 
cells  lining  the  convoluted  tubules  and  the  ascending  branches  of 
Henle's  tubes  appear  to  be  those  most  active  in  carrying  on  the 
eliminative  function  of  the  kidney. 

2.  The  pelvis  of  the  kidney  and  its  calices  are  lined  with  trans- 
itional epithelium.  It  consists  of  only  three  or  four  layers  of 
epithelial  cells  of  different  shapes.  The  most  superficial  layer  is 
composed  of  rather  large  flattened  cells,  having  ridges  upon  their 
lower  surfaces,  which  fill  the  spaces  between  the  tops  of  the  next 
layer.  This  is  made  up  of  pear-shaped  or  caudate  cells,  the  hemi- 
spherical tops  of  which  fit  into  the  cavities  between  the  ridges  on 
the  layer  above,  while  their  slender  processes  penetrate  between 

FIG.  140. 


Epithelial  cells  from  the  pelvis  of  a  human  kidney.    (Rieder.) 

the  oval  or  round  cells  that  make  up  the  deepest  layers  of  the 
epithelial  covering  (Fig.  140). 

Beneath  the  epithelium  is  a  coat  of  fibrous  tissue,  denser  near  the 
epithelium  and  more   areolar  in  its  deeper  portions.     Here  it  is 


164 


NORMAL  HISTOLOGY. 


interlaced  with   smooth    muscular   fibres,  outside  of  which  is  the 
external  coat  of  fibrous  tissue. 

3.  The   ureters   closely  resemble  in    structure  the   pelvis  of  the 
kidney;  but  the  muscular  fibres  have  a  somewhat  more  definite 
arrangement,  being  disposed  in  an  inner  imperfect  coat  of  longi- 
tudinal and  an  external  layer  of  circular  fibres,  outside  of  which 
a  few  supplementary  longitudinal  fibres  are,  here  and  there,  added 
(Fig.  141). 

4.  The  bladder  also  has  a  lining  of  transitional  epithelium  (Fig. 

FIG.  141. 


Epithelial  cells  from  the  human  ureter.    (Rieder.) 

40),  beneath  which  is  a  layer  of  fibrous  tissue  resembling  that  of 
the  renal  pelvis,  but  of  greater  thickness.  The  muscular  coat, 
which  comes  next,  is  thick  and  composed  of  bundles  of  smooth 
muscular  fibres,  interlacing  in  various  directions  or  disposed  in 
more  or  less  well-defined  strata.  External  to  the  muscular  coat 
is  a  fibrous  coat,  which  is  covered  by  a  reflection  of  the  peritoneum 
for  a  part  of  its  extent,  and  in  other  situations  passes  into  the  sur- 
rounding areolar  tissue. 

The  spear-shaped  cells  of  the  transitional  epithelium  of  the  blad- 
der have  thicker  processes  than  those  of  the  pelvis  or  ureter ;  but 
when  detached  and  macerated  in  the  urine  it  is  often  very  difficult 
to  determine  from  their  appearance  from  what  part  of  the  urinary 
tract  such  cells  were  derived  (Figs.  142  and  143). 


THE   URINARY  ORGANS. 


165 


5.  The   urethra  differs  in   structure  in   the  two  sexes.     In  the 
male  the  prostatic  portion  is  lined  with  epithelium  resembling  that 


FIG.  143. 


Epithelial  cells  from  the  mucous  membrane  of  the  human  bladder.    (Rieder.) 
Fig.  142.— From  the  urinary  sediment  from  a  case  of  cystitis,    The  cells  are  somewhat 

swollen  after  maceration  in  the  altered  urine. 
Fig.  143.— Removed  from  the  internal  surface  of  a  normal  bladder. 

of  the  bladder.     Further  forward,  it  gradually  passes  into  cylin- 
drical epithelium,  at  first  more  than  one  layer  thick ;  but  in  the 


166  NORMAL  HISTOLOGY. 

cavernous  portion  of  the  urethra  it  consists  of  but  a  single  layer. 
The  stratified  epithelium  covering  the  glans  extends  for  a  short 
distance  from  the  meatus  into  the  urethra  (Fig.  144).  The  epithe- 


FIG.  144. 


Epithelium  from  the  human  male  urethra.    (Rieder.) 

lial  lining  rests  upon  fibrous  tissue  containing  a  number  of  elastic 
fibres,  and  this  is  bounded  externally  by  a  muscular  coat.  In  the 
prostatic  portion  the  muscular  coat  consists  of  an  inner  longitudinal 
and  an  outer  circular  layer  of  fibres,  which  become  less  well  marked 
as  the  course  of  the  urethra  is  followed,  the  circular  coat  disappear- 
ing in  the  bulbous  portion  and  the  longitudinal  fibres  becoming 
scattered  toward  the  anterior  part  of  the  cavernous  portion.  The 
mucous  membrane  contains  little  tubular  glands,  "  LittrS's  glands," 
some  of  which  are  simple,  while  others  are  compounded.  In  the 
collapsed  condition  the  urethral  mucous  membrane  is  thrown  into 
one  or  more  longitudinal  folds. 

In  the  female  the  epithelial  lining  of  the  urethra  is  either  strati- 
fied or  composed  of  a  single  layer  of  columnar  cells.  The  glands 
are  more  sparsely  distributed  than  in  the  male,  except  for  a  group 
situated  near  the  meatus.  On  the  other  hand,  the  muscular  coat 
is  thicker  and  consists  throughout  the  course  of  the  urethra  of  a 
well-defined  internal  longitudinal  and  external  circular  layer  of 
fibres. 

From  the  pelvis  of  the  kidney  to  the  stratified  epithelium  of  the 


THE   URINARY  ORGANS.  167 

mcatus  the  mucous  membranes  are  capable  of  secreting  mucus,  which 
is  much  increased  in  amount  under  the  influence  of  irritating  sub- 
stances, such  as  concentrated  urine  or  the  various  causes  of  inflam- 
mation. The  bloodvessels  are  most  numerous  and  of  largest  size 
in  the  areolar  tissue  beneath  the  epithelium,  and  are  accompanied 
by  the  lymphatics.  The  nerves  are  distributed  chiefly  to  the  mus- 
cular coats,  but  also  extend  into  the  fibrous  tissue,  up  to  and  into 
the  epithelium.  The  cells  of  the  latter  are  connected  by  little 
protoplasmic  bridges,  as  in  the  case  of  the  epidermis,  leaving  minute 
channels  between  the  cells  for  the  passage  of  nutrient  fluids. 


CHAPTER   XIII. 
THE   RESPIRATORY  ORGANS. 

THE  respiratory  tract  consists  of  the  larynx,  trachea,  bronchi, 
and  lungs. 

1.  The  Larynx. — The  interior  of  the  larynx  is  lined  with  ciliated 
columnar  epithelium,  which  extends  over  the  false  vocal  cords  and 
about  half-way  up  the  epiglottis   above,  and  is   continuous  below 
with  a  similar  lining  throughout  the  trachea   and  bronchi.     This 
lining  is  interrupted  over  the  true  vocal  cords  by  a  covering  of 
stratified  epithelium,  and  at  its  upper  limits  passes  into  the  stratified 
epithelium  lining  the  buccal  cavity  and  pharynx  and  covering  the 
tongue.     Opening  upon  this  epithelial  surface,  except  upon  the  true 
vocal  cords  and  in  the  smallest  bronchi,  are  mucous  glands,  varying 
in  number  in  different  situations.     Some  of  the  columnar  cells  upon 
the  surface  are  also  mucigenous,  discharging  their  secretion  upon 
the  free  surface  of  the  mucous  membrane. 

The  thyroid,  cricoid,  and  most  of  the  arytenoid  cartilages  are 
composed  of  the  hyaline  variety  of  that  tissue :  the  epiglottis, 
cornicula  laryngis,  and  the  apices  of  the  arytenoids,  of  elastic  car- 
tilage. 

Beneath  the  epithelium  lining  the  laryngeal  ventricle  is  a  con- 
siderable layer  of  lymphadenoid  tissue.  In  other  situations  the 
epithelium  rests  upon  fibrous  tissue. 

2.  The  Trachea. — The   tracheal  wall   may  be   divided  into  four 
coats :    a,  the  mucous  membrane  ;  6,  the  subrnncous  coat ;  c,  the 
cartilage ;  d,  the  fibrous  coat  (Fig.  145). 

a.  The  mucous  membrane  is  covered  with  ciliated  columnar  epi- 
thelium resting  upon  a  nearly  homogeneous  basement-membrane, 
beneath  which  is  a  layer  of  fibrous  tissue.  This  may  be  divided 
into  two  portions :  an  outer  one,  next  to  the  basement-membrane, 
which  is  areolar  in  character,  with  a  large  admixture  of  elastic 
fibres  and  lymphadenoid  tissue,  and  an  abundant  supply  of  blood- 
vessels ;  and  an  inner  one,  less  highly  vascularized,  and  composed 
chiefly  of  elastic  fibres  running  a  longitudinal  course. 

168 


THE   RESPIRATORY  ORGANS. 


169 


b.  The  submucous  coat  is  of  areolar  fibrous  tissue,  supporting  the 
mucous  glands  that  open    into  the  trachea,  and  the    bloodvessels, 
lymphatics,  and  nerves,  and  also  little  masses  of  adipose  tissue.     In 
the  neighborhood  of  the  cartilages  this  fibrous  tissue  becomes  con- 
densed to  form  the  perichondrium. 

c.  The  cartilages  are  composed  of  the  hyaline   variety  of  that 

FIG.  145. 


From  a  longitudinal  section  through  the  trachea  of  a  child.    (Klein.)    a,  the  stratified 
columnar  ciliated  epithelium  of  the  internal  free  surface ;  b,  the  basement -membrane ; 

c,  the  mucosa  (tunica  propria) ;  d,  the  network  of  longitudinal  elastic  fibres  (the  oval  nuclei 
between  them  indicate  connective-tissue  corpuscles) ;  e,  the  submucous  tissue,  con- 
taining mucous  glands;  /,  large  bloodvessels;  g,  fat-cells:   h,  hyaline  cartilage  of  the 
tracheal  rings.    (Only  a  part  of  the  tracheal  wall  is  given  in  the  figure.) 

tissue,  and  are  incomplete  rings,  interrupted  behind,  where  the  two 
ends  are  united  by  a  band  of  smooth  muscular  tissue. 

d.  The  fibrous  coat  is  of  areolar  tissue  beyond  the  bounds  of  the 
perichondrium,   and   serves  to   connect  the  trachea  with  its  sur- 
roundings. 

3.  The  Bronchi. — The  main  bronchi  branching  from  the  trachea 
have  a  structure  similar  to  that  organ,  but  the  cartilaginous  rings 
become  more  delicate  as  the  tubes  diminish  in  size. 


170  NORMAL  HISTOLOGY. 

The  smaller  bronchi  differ  in  structure  from  the  trachea  in 
possessing  a  muscularis  mucosse,  with  its  fibres  disposed  in  a 
circular  direction,  and  having  irregular  cartilaginous  plates  in  their 
walls*,  instead  of  C-shaped,  imperfect  rings.  The  four  coats  may 
be  enumerated  as  follows  : 

a.  Mucous  membrane,  covered  with  ciliated  columnar  epithelium 
resting  upon  a  basement-membrane,   beneath   which   is   a   fibrous 
tissue  containing  numerous  elastic  fibres  lying  parallel  to  the  axis 
of  the  bronchus.     Under  this  are  the  circular  fibres  of  the  mus- 
cularis mucosae. 

b.  Submucous  coat,  similar  to  that  of  the  trachea  and  larger 
bronchi. 

c.  Cartilaginous  coat,  containing  the  plates  of  cartilage  that  sup- 
port the  walls. 

d.  Fibrous  coat  of  areolar  tissue,  containing  a  little  adipose  tissue 
and  passing  into  the  areolar  tissue  of  neighboring  structures. 

As  the  bronchi  subdivide  and  become  smaller  the  coats  get 
thinner,  and  first  the  cartilaginous  and  then  the  muscular  coat  dis- 
appears. Those  air-passages  which  are  without  cartilage,  but  have 

FIG.  146. 


Portion  of  a  cross-section  of  a  bronchiole  from  the  lung  of  a  pig.  (Schultze.)  a,  areolar 
external  coat ;  b,  muscularis  mucosse ;  c,  subepithelial  areolar  tissue,  containing  numerous 
longitudinal  elastic  fibres,  represented  here  in  cross-section ;  d,  ciliated  epithelium,  form- 
ing the  most  superficial  layer  of  the  mucous  membrane  ;  /,  walls  of  the  neighboring  pul- 
monary alveoli.  In  these  walls  branching  and  anastomosing  elastic  fibres  are  shown ; 
the  capillary  plexus  has  been  omitted. 

a  muscularis  mucosse,  are  called  "bronchioles"  (Fig.  146).  The 
still  smaller  branches,  which  have  lost  their  muscular  tissue,  are 
known  as  the  "alveolar  passages."  In  the  latter  the  columnar 


Till':  UMPIRATORY  ORGANS. 


171 


epithelium  lining  the  bronchi  gives  place  to  a  pavement-epithelium, 
composed  of  small  flattened  cells  disposed  in  a  single  layer.  The 
elastic  tissue  of  the  mucous  membrane  is  continued  through  all  the 
divisions  of  the  air-passages,  and  becomes  a  constituent  part  of  the 
alveolar  walls  of  the  lung  itself. 

The  alveolar  passages  open  into  spaces,  called  the  "  infundibula," 
in  the  sides  of  which  are  the  openings  into  the  alveoli  of  the 
lung,  the  ultimate  destination  of  the  inspired  air.  Here  and  there 


Section  of  lung  of  the  dog,  showing  a  transverse  section  of  a  bronchiole:  a,  bronchiole  (a 
little  mucus  covers  the  epithelial  lining) ;  6,  muscular  layer  of  the  mucous  membrane ;  c, 
c,  radicles  of  the  pulmonary  vein ;  d,  alveolar  passage*  just  at  its  division  to  form  infun- 
dibula. An  infundibulum  extends  from  this  passage  toward  the  bronchiole.  The  wall 
of  the  alveolar  passage  at  this  point  is  similar  in  structure  to  that  of  the  pulmonary 
alveoli,  e,  alveolar  passage  in  oblique  section.  This  passage  is  cut  at  a  point  further 
from  its  opening  into  the  infundibula,  and  has  a  somewhat  thicker  wall  than  d.  The  rest 
of  the  section  is  made  up  of  infundibula  (the  larger  spaces)  and  pulmonary  alveoli. 

stray  alveoli  open  directly  into  the  alveolar  passages  (Figs.   147, 
148*  and  149). 

4.  The  pulmonary  alveoli  and  the  smaller  air-passages  are  so 
arranged  that  there  are  no  vacant  spaces  ;  and  neighboring  alveoli, 
whether  they  belong  to  a  group  of  infundibula  springing  from 
the  same  alveolar  passages  or  to  separate  groups,  are  so  closely 
situated  that  they  have  but  one  common  wall  dividing  their  cavities 


172 


NORMAL  HISTOLOGY. 


from  each  other.  Notwithstanding  this  general  compactness  of 
arrangement,  the  lungs  are  divided  by  delicate  septa  of  fibrous 
tissue  into  more  or  less  well-defined  lobules,  corresponding  to  the 
smallest  bronchi  or  the  bronchioles. 

The  alveolar  walls  are  made  up  of  a  delicate,  loose  areolar  tissue, 
containing  numerous  elastic  fibres  and  supporting  the  abundant 
capillary  plexus  in  which  the  blood  suffers  the  gaseous  exchanges 
with  the  air  that  constitute  the  function  of  respiration  (Fig.  150). 

FIG.  148. 


Section  of  lung  of  the  dog :  o,  alveolar  passage  opening  into  an  infundibulum  and  also  into 
a  solitary  alveolus  ;  b,  cross-section  of  an  infundibulum.  The  dotted  line  indicates  the 
limits  of  the  infundibular  space.  Opening  into  it  are  a  number  of  alveoli.  Were  the 
dotted  line  removed,  the  infundibular  cross-section  and  the  alveoli  around  it  would  form 
a  stellate  space  in  the  section,  c,  junction  of  two  radicles  of  the  pulmonary  vein.  At 
the  top  of  the  section,  to  the  right,  is  an  oblique  section  of  a  bronchiole. 

Covering  the  two  surfaces  of  the  alveolar  wall  is  a  layer  of  very 
thin  cellular  plates  (pavement-epithelium,  see  Fig.  30),  among 
which  are  scattered  a  few  cells  resembling  those  lining  the  alveolar 
passages.  ,  This  cellular  investment  is  continuous  with  the  lining 
of  the  infundibulum,  which  is  of  similar  character,  and  thence  with 
the  epithelium  covering  the  inner  surface  of  the  alveolar  passage. 
It  is  to  be  regarded  as  a  special  modification  of  epithelium,  fitting 
it  for  usefulness  in  this  situation. 


THE  RESPIRATORY  ORGANS. 


173 


The  lung  receives  blood  from  two  sources :  1,  venous  blood, 
through  the  pulmonary  artery,  which  is  oxygenated  in  the  walls  of 
the  alveoli ;  2,  arterial  blood,  through  the  bronchial  arteries.  This 
arterial  blood  serves  for  the  nourishment  of  the  tissues  of  the  lung 
and  is  distributed  to  the  bronchi,  interlobular  connective  tissue, 
lymph-glands,  and  walls  of  the  vessels.  Part  of  this  blood  returns 
through  the  pulmonary  veins;  the  rest  through  the  bronchial  veins. 

FIG.  149. 


c:  ---d 


Section  of  lung  of  the  dog:  a,  oblique  section  of  a  bronchiole ;  6,  its  muscular  coat ;  c,  longi- 
tudinal section  of  an  infundibulum.  communicating  to  the  right  with  an  alveolar  passage 
(the  wall  of  the  latter  is  torn  further  to  the  right) ;  d,  one  of  the  alveoli  opening  into  c. 

The  lymphatics  arise  in  the  walls  of  the  alveoli  and  bronchi  and 
pass  to  the  bronchial  lymph-glands. 

The  nerves  supplying  the  lung  may  be  traced  along  the  bronchi, 
where  they  occasionally  connect  with  groups  of  ganglion-cells,  and 
along  the  vessels.  They  are  of  both  the  medullated  and  the  non- 
medullated  varieties. 

The  surface  of  the  lung  is  covered  with  serous  membrane,  a  por- 
tion of  the  pleura. 

Little  need  be  said  about  the  functional  activity  of  the  lung. 
The  cilia,  belonging  to  the  columnar  epithelium  lining  nearly  the 


174  NORMAL  HISTOLOGY. 

whole  of  the  air-passages,  possess  a  motion  that  urges  particles 
lodging  in  the  mucus  covering  them  toward  the  larynx,  whence 
they  are  either  coughed  out  or  are  swallowed.  Such  solid  particles 
as  pass  beyond  the  regions  guarded  by  ciliated  epithelium  are  taken 
up  by  leucocytes,  which  frequently  migrate  into  the  alveoli  and  the 
air-passages,  and  are  conveyed  by  them  into  the  lymphatic  vessels 
or  glands.  Because  of  this  the  lymphatics  and  bronchial  lymphatic 
nodes  are  apt  to  be  blackened  by  the  deposition  of  carbon,  except 
in  young  individuals.  The  flow  of  air  into  the  lung  is  the  result  of 
atmospheric  pressure,  which  tends  to  fill  the  thoracic  cavity  when  the 

FIG.  150. 


Section  of  the  lung  of  a  dog,  killed  by  ether-narcosis.  The  lung  was  hypergemic  at  the  time 
of  death,  and  the  capillaries  retain  their  blood  in  the  section,  a,  alveolus  in  cross-sec- 
tion, communicating  with  the  infundibulum,  6.  A  portion  of  the  wall  of  the  alveolus  is 
seen,  in  surface-view,  at  c.  d,  e,  other  alveoli  opening  into  the  same  infundibulum ;  /, 
cross-section  of  an  infundibulum  with  alveoli  opening  into  it;  g,  surface-aspect  of  an 
alveolar  wall,  showing  capillary  plexus  filled  with  red  blood-corpuscles. 

chest  is  expanded  through  the  action  of  the  muscles  of  respiration. 
The  air  is  expelled  from  the  lungs  when  those  muscles  relax,  partly 
because  of  the  pressure  exerted  by  the  thoracic  walls,  but  chiefly 
because  of  the  contraction  of  the  elastic  fibres  in  the  alveolar  walls. 


THE  RESPIRATORY  ORGANS.  175 

Because  of  their   presence   the    lungs    retract  when   the   chest  is 
opened. 

When  sections  of  the  lung  are  examined  under  the  microscope 
it  is  difficult,  at  first,  to  identify  the  different  portions,  which  are 
cut  in  all  directions.  The  smaller  bronchi  may  be  recognized 
by  the  presence  of  cartilage  in  their  walls.  The  bronchioles  pos- 
sess no  cartilage,  but  are  surrounded  by  a  band  of  smooth  mus- 
cular tissue,  the  muscularis  mucosae.  This  becomes  thinner,  then 
incomplete,  and  finally  disappears  as  the  infundibula  are  reached. 
The  infundibulum,  it  will  be  remembered,  is  the  space  into  which 
the  alveoli  open.  When  seen  in  section  it  will  appear  as  a  round, 
oval,  or  elongated  space,  according  to  the  direction  in  which  it 
has  been  cut,  bounded  by  scallops,  each  of  which  is  the  cavity  of 
an  alveolus.  In  every  section  there  will  be  many  alveoli  which 
have  been  so  cut  that  their  openings  into  the  infundibulum  will  not 
be  included  in  the  section.  These  alveoli  have  a  continuous  wall 
surrounding  their  cavities.  Still  other  alveoli  will  have  been  cut 
in  such  a  way  that  a  portion  of  their  walls  will  lie  in  the  plane  of 
the  section  and  parallel  to  it,  so  that  the  flat  surface  of  the  alveolar 
wall  will  be  visible,  surrounded  by  an  oblique  or  cross-section,  where 
the  wall  meets  the  surface  of  the  section.  Those  alveolar  walls  which 
have  been  cut  perpendicular  to  their  surfaces  will  appear  thinner 
than  those  which  have  been  cut  obliquely.  With  these  considera- 
tions in  his  mind,  the  student  can  have  little  difficulty  in  identify- 
ing the  different  portions  of  the  section  (see  Figs.  147-150). 


CHAPTER   XIV. 
THE  SPLEEN. 

NEARLY  the  whole  surface  of  the  spleen  is  invested  with  a  cov- 
ering of  peritoneum  similar  to  that  which  partially  covers  the 
liver.  Beneath  this  is  the  true  capsule  of  the  spleen,  which  com- 
pletely surrounds  it.  This  capsule  is  composed  of  dense  fibrous 
tissue,  containing  a  large  number  of  elastic  fibres  and  a  few  of 
smooth  muscular  tissue.  From  its  inner  surface  bands  of  the  same 
tissue,  called  the  "  trabeculse,"  penetrate  into  the  substance  of  the 
organ,  where  they  branch,  and  the  branches  join  each  other  to  form 
a  coarse  meshwork  occupied  by  the  parenchyma  of  the  organ,  the 
u  pulp." 

The  bloodvessels  of  the  spleen  enter  at  the  hilum  and  pass  into 
the  large  trabeculse,  which  start  from  the  capsule  at  that  point 
and  enclose  the  vessels  until  they  divide  into  small  branches.  The 
vessels  then  leave  the  trabeculse  and  penetrate  the  pulp,  where  they 
break  up  into  capillaries,  which  do  not  anastomose  with  each  other. 
There  is  some  doubt  as  to  the  way  in  which  these  capillaries  end. 
According  to  one  view,  they  unite  to  form  the  venous  radicles,  so 
that  the  blood  is  confined  within  vessels  throughout  its  course  in  the 
spleen.  Another  view,  which  is  more  probably  correct,  is  that  the 
walls  of  the  capillaries  become  incomplete,  clefts  appearing  between 
their  endothelial  cells,  which  finally  change  their  form  and  become 
similar  to  those  of  the  reticulum  of  the  pulp.  The  veins,  accord- 
ing to  this  view,  arise  in  a  manner  similar  to  the  endings  of  the 
arteries.  The  result  of  this  structure  would  be  that  the  blood  is 
discharged,  from  the  capillary  terminations  of  the  arteries,  directly 
into  the  meshes  of  the  pulp,  after  which  it  is  taken  up  by  the 
capillary  origins  of  the  veins  (Figs.  151  and  152). 

The  pulp  consists  of  a  fine  reticulum  of  delicate  fibres  and  cells, 
with  branching  and  communicating  processes,  in  the  meshes  of 
which  there  are  red  blood-corpuscles,  leucocytes  in  greater  number 
than  normally  present  in  the  blood,  and  free  amoeboid  cells  consid- 
erably larger  than  leucocytes,  called  the  "  splenic  cells." 

176 


THE  SPLEEN. 


177 


The  adventitia  of  the  arteries  contains  considerable  lymphadenoid 
tissue,  which  after  the  exit  of  the   vessels  from  the  trabecute  is 


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Section  from  the  spleen  of  the  cat.    (Bannwarth.)    Termination  of  an  arterial  capillary  in 

the  pulp. 

expanded  at  intervals  to  form  spherical  bodies,  about  1  mm.  in  diam- 
eter, called  the  "  Malpighian  bodies  "  or  "  corpuscles."     These  are 

FIG.  152. 


Section  from  the  spleen  of  the  cat.    (Bannwarth.)    Beginning  of  a  capillary  venous  radicle. 

like  little  lymph-follicles,  through  which  the  artery  takes  its  course. 
The  reticulum  in  these  Malpighian  corpuscles  is  scanty  and  incon- 


178  NORMAL  HISTOLOGY. 

spicuous  near  their  centres,  so  that  the  lymphoid  cells  it  contains 
appear  densely  crowded  ;  but  toward  their  peripheries  the  reticulum 
is  more  pronounced  and  the  cells  a  trifle  more  separated.  At  the 
surface  of  the  Malpighian  body  its  reticulum  becomes  continuous 
with  that  of  the  pulp  surrounding  it  (Fig.  153). 

FIG.  153. 


Section  from  human  spleen.  (Kolliker.)  A,  capsule ;  b,  b,  trabeculse ;  c,  c,  Malpighian  bodies 
(lymph-follicles),  traversed  by  arterial  twigs.  In  the  follicle  to  the  left,  part  of  the 
arterial  twig  is  seen  in  longitudinal  section ;  in  that  to  the  right,  it  appears  in  cross- 
section  to  the  right  of  the  centre  of  the  follicle,  d,  arterial  branches ;  e,  splenic  pulp. 
The  section  is  taken  from  an  injected  spleen. 

The  relations  between  the  spleen  and  the  blood  flowing  through 
it  appear  to  be  very  similar  to  those  between  the  lymphatic  glands 
and  the  lymph  passing  through  them.  It  seems  to  act  as  a  species 
of  filter,  in  which  foreign  particles  or  damaged  red  blood-corpuscles 
are  arrested  and  destroyed.  In  many  infectious  diseases  the  splenic 
pulp  is  increased  in  amount  and  highly  charged  with  granules  of 
pigment  that  appear  to  be  derived  from  the  coloring-matter  of  the 
blood.  This  is  notably  the  case  in  malaria,  in  which  the  red  cor- 
puscles are  destroyed  by  the  plasmodium  occasioning  the  disease. 
When  bacteria  gain  access  to  the  blood  they  are  apt  to  be  especially 
abundant  in  the  splenic  pulp,  and  it  is  said  that  monkeys,  which 
are  normally  immune  against  relapsing  fever,  may  acquire  the  dis- 
ease if  the  spleen  be  removed  before  inoculation  with  the  spirillum 


THE  SPLEEN.  179 

which  is  the  cause  of  that  disease.  These  observations  all  tend  to 
confirm  the  view  that  the  function  of  the  spleen  is  to  assist  in  main- 
taining the  functional  integrity  of  the  blood.  The  lymphadenoid 
tissue  within  the  spleen  also  enriches  the  blood  with  an  additional 
number  of  leucocytes. 


CHAPTER  XV. 


THE  DUCTLESS  GLANDS. 

THE  organs  included  in  this  group  possess,  at  some  stage  of  their 
development  or  in  the  adult,  a  structure  analogous  to  that  of  the 
secreting  glands.  Those  which  retain  this  structure  after  complete 
development  differ  from  the  other  glandular  organs  in  being  devoid 
of  ducts,  through  which  the  materials  elaborated  by  their  paren- 
chyma could  be  discharged.  Of  these  organs  the  thyroid  is  the  most 
striking  example.  Other  members  of  this  group,  notably  the  thy- 
mus,  become  greatly  modified  as  development  advances,  and  after  a 

FIG.  154. 


Section  of  human  thyroid  gland :  a,  alveolus  filled  with  colloid  ;  b,  alveolus  containing  a 
serous  fluid ;  c,  interalveolar  areolar  tissue ;  d,  tangential  section  of  an  alveolus,  giving 
a  superficial  view  of  the  epithelial  cells. 

while  retain  mere  vestiges  of  their  original  epithelial  character ; 
the  chief  bulk  of  the  organ  being  composed  of  lymphadenoid 
tissue. 

The  following  organs  and  structures  will  be  considered  as  belong- 
ing to  the  general  group  of  ductless  glands  :  the  thyroid  gland,  the 

ISO 


THE  DUCTLESS  GLANDS.  181 

parathyroids,  the  adrenal  bodies,  the  pituitary  body,  the  thymus, 
and  the  carotid  and  coccygeal  bodies. 

1.  The  Thyroid  Gland  (Fig.  154). — This  consists  of  a  number 
of  alveoli  or  closed  vesicles,  lined  with  cubical  epithelial  cells  ar- 
ranged in  a  single  layer  upon  the  delicate,  vascularized  areolar  tissue 
which  forms  their  walls  and  separates  the  neighboring  alveoli  from 
each  other.  This  fibrous  tissue  is  more  abundant  in  places,  where 
it  serves  to  divide  the  gland  into  a  number  of  imperfectly  defined 
lobes.  At  the  periphery  of  the  organ  its  connective  tissue  becomes 
continuous  with  a  thin  but  moderately  dense  fibrous  capsule. 

The  individual  alveoli  differ  both  in  respect  to  their  size  and  their 
contents.  Many  are  more  or  less  completely  filled  with  a  nearly 
homogeneous,  glairy  substance,  of  a  slight  yellowish  tint,  called 
"colloid,"  while  others  appear  to  be  occupied  by  a  serous  fluid. 

FIG.  155.  FIG.  156. 


Sections  of  thyroid  gland.    (Schmid.) 
Fig.  155.— From  a  dog :  a,  colloid  or  secreting  cells ;  b,  reserve  cells  (these  differ  only  in  their 

states  of  activity) ;  c,  cells  containing  less  colloid  than  a. 
Fig.  156. — From  a  cat :  a,  daughter-cells  arising  from  the  division  of  an  epithelial  cell. 

The  elaboration  of  this  colloid  material  seems  to  be  the  function 
of  the  organ,  though  it  may  have  other  less  obvious  duties. 

The  cells  lining  the  alveoli  may  be  divided  into  two  classes, 
which  differ  in  appearance  (Fig.  155):  first,  those  engaged  in  the 
production  of  colloid,  secreting  cells ;  and,  second,  those  in  which 
no  colloid  is  present,  and  which  are  regarded  as  reserve  cells. 
The  latter  are  capable  of  multiplication,  thereby  replacing  such  of 


182 


NORMAL  HISTOLOGY. 


the  secreting  cells  as  may  be  destroyed  (Fig.   156).     The  colloid 
material  is  produced  within  the  cytoplasm  of  the  secreting  cells, 


FIG.  157. 


'^fM^^PHPHBI 

Section  from  thyroid  of  dog,  illustrating  the  egress  ot  colloid  from  the  alveoli.  (Bozzi.) 
a,  epithelial  cells  lining  the  alveolus,  seen  in  section.  The  internal  ends  of  similar  cells 
are  seen  in  superficial  aspect  below.  6,  colloid  within  the  alveolus ;  c,  exit  of  colloid 
between  two  epithelial  cells  ;  e,  lymphatic  vessel ;  d,  end  of  a  colloid  or  secreting  cell  in 
the  epithelial  lining  of  the  alveolus. 

whence  it  is  either  expelled  into  the  lumen  of  the  alveolus,  or  the 
whole  cell  becomes  detached  from  the  alveolar  wall  and  suffers  col- 

FIG.  158. 


Section  from  thyroid  of  dog,  illustrating  the  egress  of  colloid  from  the  alveoli.  (Bozzi.) 
a  epithelial  lining  of  the  alveolus  ;  b,  colloid ;  c,  escape  of  colloid  through  a  defect  in  the 
wall  occasioned  by  the  colloid  metamorphosis  of  some  of  the  epithelial  cells,  the  nuclei 
of  which  are  discernible  within  the  colloid  near  c. 

loid   degeneration,    with    destruction    of  the    nucleus,    within    the 
alveolar  cavity. 


THE  DUCTLESS  GLANDS.  183 

The  colloid  material  subsequently  finds  its  way  into  the  general 
circulation,  either  by  passing  between  the  intact  cells  of  the  alveolus 
(Fig.  157),  or  after  a  passage  has  been  prepared  for  it  through  altera- 
tions in  certain  of  those  cells  (Fig.  158).  The  colloid  is  then  taken 
up  by  the  lymphatics,  through  which  it  reaches  the  general  circula- 
tion. This  is  an  example  of  internal  secretion  which  presents  much 
of  interest.  It  is  probable  that  a  similar,  but  much  less  obvious, 
process  takes  place  in  some  of  the  ordinary  secreting  glands  of  the 
body,  certain  elaborated  materials  being  returned  to  the  circulation 
by  the  cells  of  the  gland,  while  others  are  utilized  for  their  nourish- 
ment and  for  the  elaboration  of  the  more  obvious  secretion. 

That  the  secretion  of  the  thyroid  gland  is  of  importance  to  the 
general  organism  is  shown  by  the  effects  of  disease  or  removal  of 
the  gland  upon  the  general  nutrition.  Total  extirpation  of  the 
thyroid,  together  with  the  parathyroids,  occasions  the  death  of  an 
animal  within  a  few  days,  after  symptoms  of  grave  disturbances  in 
the  central  nervous  system,  among  which  are  tetanic  convulsions. 
A  partial  removal  of  the  gland,  or  its  removal  without  that  of  the 
parathyroids,  causes  profound  disturbances  of  nutrition,  grouped 
under  the  title  "  cachexia  strumipriva."  The  animal  becomes  weak, 
drowsy,  and  emaciated ;  the  skin  dry  and  scaly,  with  a  loosening 
of  the  hairs.  In  young  animals  the  growth  is  retarded,  especially 
the  development  of  the  bones,  through  degenerative  changes  in  the 
epiphysial  cartilages.  In  these,  the  intercellular  substance  becomes 
swollen  and  disintegrated  ;  the  cells  atrophied  or  destroyed.  Marked 
changes,  designated  as  myxredema,  also  appear  in  the  subcutaneous 
tissue,  which  is  converted  into  a  species  of  mucoid  tissue,  probably 
as  the  result  of  an  altered  metabolism  within  the  pre-existent  cells 
of  the  tissue.  The  functional  activity  of  the  kidney  is  modified ; 
after  a  while,  albuminuria  results.  Exactly  similar  disturbances  have 
been  observed  in  people  suffering  from  disease  of  the  thyroid  gland. 

The  foregoing  facts  are  cited  here  in  order  to  emphasize  by  a 
striking  example  the  statement  previously  made,  that  the  organs  of 
the  body  are  mutually  dependent  upon  each  other. 

Experimentation  and  clinical  study  have  further  shown  that  the 
symptoms  of  myxoedema  may  be  moderated  or  perhaps  entirely 
arrested  by  feeding  with  thyroid  extracts,  or  still  more  markedly 
by  injecting  extracts  from  thyroid  glands  beneath  the  skin,  where 
they  would  speedily  pass  into  the  lymphatics  and  thence  into  the 
general  circulation. 


184  NORMAL  HISTOLOGY. 

Chemical  examination  has  revealed  the  presence  of  a  substance 
called  "  thyroiodin  "  in  the  alveoli  of  the  thyroid  gland.  This  is  a 
proteid  containing  a  large  amount  of  iodine.  Its  production  by  the 
thyroid  gland  may  be  increased  by  feeding  with  substances  contain- 
ing considerable  iodine  or  by  administering  iodide  of  potassium. 
Injections  of  thyroiodin  serve  to  mitigate  the  effects  of  thyroidec- 
tomy,  very  much  as  do  injections  of  thyroid  extracts.  It  is  by  no 
means  clear,  however,  that  the  thyroiodin  is  the  only  substance 
elaborated  by  the  thyroid  gland  which  may  be  of  use  to  the  tissues 

FIG.  159. 


o 

Section  of  the  thyroid  gland  of  a  kitten  two  months  old.  (Kohn.)  Showing  the  positions 
of  the  outer  and  inner  parathyroid  bodies  and  a  thymus  follicle :  t,  thyroid  gland  ;  p, 
inner  parathyroid;  p',  outer  parathyroid;  th,  thymus  follicle;  a,  portion  of  the  section 
showing  the  intimate  relations  between  the  thyroid  and  the  inner  parathyroid ;  6,  por- 
tion demonstrating  a  similar  intimate  relation  between  the  thyroid  and  the  tissues  of  the 
thymus  follicle. 

of  other  organs,  or  that  the  thyroid  may  not  also  remove  injurious 
substances  from  the  circulation  and  thus  indirectly  benefit  other 
structures  in  the  body.1 

1  Attention  is  also  called  to  the  possibility  that  an  excessive  or  morbid  thyroid 
secretion  may  cause  symptoms  of  disease  attributable  to  disturbances  in  the  functions 
of  other  organs,  and  may  also  occasion  disturbances  in  nutrition. 


THE  DUCTLESS  GLANDS. 


185 


The  bloodvessels  of  the  thyroid  are  abundant,  and  form  a  rich 
plexus  in  the  areolar  tissue  between  the  alveoli.  The  lymphatics 
are  also  abundant  and  large,  forming  a  network  of  rather  large  ves- 
sels in  the  same  situation.  The  nerves  accompany  the  vessels,  are 
destitute  of  ganglia,  and  have  been  traced  to  the  bases  of  the  epi- 
thelial cells,  whence  they  may  occasionally  send  minute  terminal 
twigs  with  enlarged  ends  between  the  epithelial  cells. 

2.  The  Parathyroids  (Figs.  159,  160,  161).— These  are  two  bodies 

FIG.  160. 


Section  of  a  portion  of  the  external  parathyroid  of  a  kitten  two  months  old.  (Kohn.)  Show- 
ing the  columns  of  epithelial  cells  separated  by  a  delicate,  vascular  areolar  tissue.  The 
nuclei  between  the  columns  of  epithelium  belong  chiefly  to  capillary  bloodvessels,  m, 
m,  nuclei  exhibiting  karyokinetic  figures. 


of  identical  structure,  which  are  developed  in  conjunction  with 
the  thyroid  gland ;  but,  while  the  latter  progresses  in  its  devel- 
opment until  it  attains  the  structure  already  described,  the  para- 
thyroids retain  a  structure  similar  to  that  of  the  embryonic  thyroid. 
They  are  composed  of  solid  columns  of  epithelial  cells,  which  anas- 
tomose with  each  other,  but  are  elsewhere  separated  by  a  small 
amount  of  vascular  areolar  tissue.  They  are  enclosed  in  a  very 
thin  capsule  of  areolar  tissue,  but  are  in  very  close  relation  to  the 
neighboring  tissues  of  the  thyroid  gland  (Figs.  159  and  161),  and 
frequently  also  with  isolated  follicles  of  thymus  tissue. 

Different  observers  vary  in  their  opinions  respecting  the  para- 
thyroids. Some  regard  them  as  reserve  thyroid  tissue,  remaining 
dormant  while  the  thyroid  is  functionally  competent,  but  developing 


186 


NORMAL  HISTOLOGY. 


into  thyroid  tissue  when  the  gland  furnishes  an  insufficient  supply  of 
secretion.  Other  observers  deny  this  and  regard  the  parathyroids 
as  embryonic  rudiments,  nearly,  if  not  quite,  devoid  of  function.  It 
is  certain  that  in  some  cases  of  thyroidectomy  the  parathyroids 
become  enlarged,  and  that  the  cachexia  strumipriva  is  not  certain  to 
develop  after  the  removal  of  the  thyroid  gland  unless  the  parathy- 

FIG.  161. 


-n 


Section  of  the  inner  parathyroid  of  a  kitten  two  months  old.  (Kohn.)  Showing  its  close 
connection  with  the  tissues  of  the  thyroid  gland :  Sch,  alveoli  of  the  thyroid ;  P,  epithelial 
columns  of  the  parathyroid  ;  K,  capsule  separating  the  two. 

roids  are  also  removed.  Histological  studies  of  the  parathyroids  in 
such  cases  have,  however,  failed  to  reveal  a  tendency  on  their  part 
to  develop  into  true  thyroid  tissue.  Their  relations  to  the  thyroid, 
therefore,  still  remain  undetermined. 

In  some  animals — e.  g.,  the  cat — there  are  four  parathyroid  bodies, 
two  associated  with  each  lobe  of  the  thyroid. 

3.  The  Adrenal  Bodies  (Fig.  162). — The  adrenal  bodies,  or  supra- 
renal capsules,  possess  a  fibrous  capsule,  which  is  more  areolar 
externally,  where  it  frequently  merges  into  the  perinephric  fat, 


THE  DUCTLESS  GLANDS. 


187 


FIG.  162. 


and  denser  internally,  where  it  is  reinforced  in  some  animals  by 
smooth  muscular  fibres.  From 
this  capsule  septa  of  areolar  tissue 
penetrate  into  the  substance  of  the 
organ  and  constitute  its  interstitial 
tissue.  The  parenchyma  of  the 
organ  consists  of  columns  of  epi- 
thelial cells,  which  are  differently 
arranged  and  have  a  somewhat  dif- 
ferent appearance  in  different  parts. 
As  the  result  of  these  differences  the 
organ  has  been  divided  into  a  cor- 
tical and  a  medullary  portion. 

In  the  cortical  portion  the  cells 
are  arranged  in  solid  columns  hav- 
ing their  long  axes  perpendicular  to 
the  surface  of  the  organ.  Toward 
the  capsule  these  columns  lose  their 
parallel  arrangement  and  appear  in 
vertical  sections  as  islets  of  cells 
surrounded  by  areolar  tissue,  the 
"  zona  glomerulosa."  In  the  deep 
portion  of  the  cortex  the  cellular 
columns  form  a  meshwork  and  com- 
pletely lose  their  fascicular  arrange-  Vertlcal"^"n  of  hum7n^enai  body. 

ment.       This     region     is    Called     the        (Eberth.)     1,  cortex;  2,  medulla;  a, 

..      T      .     ,,       rrn  -,i     T    i        capsule ;  5,  zona  glomerulosa ;  c,  zona 

ZOlia  retlClllans."       The    epithelial        fasciculata;    d,    zona   reticularis;    «, 

cells  in  the  cortical  portion  are  poly-      ^OUPS  of  medullary  ceils ;  /,  partial 

.!•«..,        section  of  a  large  vein. 

nedral,  and  are  frequently  infiltrated 

with  numerous  globules  of  oil  or  fat,  which  give  that  part  of  the 

organ  a  yellow  color. 

In  the  medulla  the  interstitial  tissue  of  the  organ  encloses  groups 
of  epithelial  cells,  which  differ  from  those  of  the  cortex  in  being 
free  from  fat.  They  are  also  larger  than  those  cortical  cells  which 
contain  no  fat  (Fig.  163). 

The  arteries  of  the  adrenal  bodies  enter  as  numerous  small  twigs 
at  the  surface  of  the  organ  and  divide  into  capillaries  within  its 
fibrous  septa.  These  open  into  a  venous  plexus  in  the  medulla, 
which  communicates  with  a  single  vein  leaving  the  organ. 

The  nervous  supply  of  the  adrenal  bodies  is  very  abundant.    The 


188 


NORMAL  HISTOLOGY. 
FIG.  163. 

-4b£.-.M 


Section  through  the  boundary  between  cortex  and  medulla  in  the  adrenal  body  of  the  horse. 
(Dostoiewsky.)  /,/,/,  cells  of  the  cortex,  infiltrated  with  fat-globules ;  g,  ganglion-cells ; 
m,  epithelial  cells  of  the  medulla. 

nerve-fibres  are  chiefly  of  the  medullated  variety,  and  their  bundles 
contain  numerous  ganglia  before  entering  the  organ.  Here  the 
fibres  ramify  abundantly  in  the  cortex,  whence  they  penetrate  into 

FIG.  164. 


Injected  lymphatics  in  an  adrenal  body  of  the  ox.  (Stilling.)  L,  injection-mass  within  the 
lymphatic  vessels ;  N,  cross-section  of  a  nerve :  V,  longitudinal  section  of  a  vein. 
Lymphatic  radicles  are  seen  among  the  epithelial  cells  (cortical  variety  free  from  fat) 
to  the  right  of  the  figure. 

the  medulla.       At  the   junction   of  the  medulla  and   cortex  the 
nerve-fibres  are  connected  with  ganglion-cells.     The  nerve-termi- 


THE  DUCTLESS  GLANDS.  189 

nations  arc  distributed  to  the  walls  of  the  vessels  and  penetrate 
between  the  epithelial  cells  of  the  parenchyma. 

As  in  the  case  of  the  thyroid  gland,  the  relations  of  the  epithelial 
cells  of  the  adrenal  bodies  to  the  lymphatics  appear  of  special 
interest.  The  lymphatic  vessels  are  abundant  and  large,  and  accom- 
pany the  bloodvessels  lying  in  the  areolar  tissue  of  the  septa. 
Here  they  come  into  close  relations  with  the  columns  of  epithelial 
cells,  and,  at  least  in  the  cortex,  send  minute  terminal  branches 
into  those  columns,  where  they  end  among  the  epithelial  cells  (Fig. 
164).  This  arrangement  of  the  lymphatics  appears  to  point  to  the 
elaboration  of  an  internal  secretion  as  the  function  of  the  adrenal 
bodies.  Small  masses  of  lymphadenoid  tissue  are  occasionally 
observed  in  the  cortical  portion  of  the  adrenal  body. 

4.  The  Pituitary  Body. — The  pituitary  body  (hypophysis  cerebri) 
is  divisible  into  two  portions,  which  differ  both  in  their  structure 
and  in  their  embryonic  origins.  The  posterior,  or  nervous,  lobe  is 
derived  from  a  prolongation  of  the  third  cerebral  ventricle.  The 
anterior,  or  glandular,  lobe  develops  from  a  tubular  prolongation, 
lined  with  epithelial  cells,  from  the  buccal  cavity  of  the  embryo. 
This  partially  or  completely  invests  the  nervous  portion  of  the 
body,  but  its  chief  bulk  is  situated  in  front.  The  connection  with 
the  buccal  cavity  is  obliterated,  and,  in  the  further  development  of 
the  detached  portion,  a  number  of  anastomosing  columns  of  epi- 
thelial cells  are  formed,  which  are  separated  from  each  other  by 
septa  of  vascular  areolar  tissue.  These  septa  become  continuous 
at  the  periphery  with  a  thin  fibrous  capsule  furnished  by  the  pia 
mater. 

The  cells  of  the  epithelial  strands  in  the  glandular  lobe  appear 
to  be  of  two  sorts,  which,  like  those  in  the  thyroid  gland,  probably 
represent  different  stages  of  functional  activity.  The  darker  sort 
of  cell  yields  microchemical  reactions  resembling  those  of  colloid ; 
and  little  masses  of  colloid,  presumably  derived  from  those  cells, 
are  of  not  infrequent  occurrence  within  or  at  the  margins  of  the 
epithelial  columns  (Figs.  165  and  166). 

The  glandular  lobe  is  richly  supplied  with  capillary  bloodvessels 
in  intimate  relations  with  the  epithelium,  from  which  they  often 
appear  to  be  separated  by  only  a  thin  basement-membrane,  and  the 
existence  of  this  is  doubtful  in  some  situations  (Fig.  167). 

The  above  description  shows  that  the  structure  of  the  hypophysis 
is  similar  to  that  of  the  other  ductless  glands  already  considered. 


190 


NORMAL  HISTOLOGY. 
FIG.  165. 


Section  from  the  hypophysis  of  the  ox.  (Dostoiewsky.)  v,  veins ;  a,  alveoli  or  cell-columns, 
with  pale,  relatively  clear  cytoplasm;  b,  alveoli  or  columns  of  darker  granular  cells. 
Other  cell-groups  contain  both  varieties  of  cell. 


FIG.  166. 


Section  from  the  glandular  lobe  of  the  hypophysis ;  horse.  (Lothringer.)  Showing  the 
darker  cells  at  the  periphery  of  the  epithelial  strands,  and  the  clearer  cells,  for  the  most 
part,  in  their  centres. 


THE  DUCTLESS  GLANDS. 


191 


Its  function  is  still  very  obscure  ;  but  it  appears,  in  cases  of  experi- 
mental thyroidectomy  and  in  disease  of  the  thyroid  in  the  human 
subject,  to  enlarge  when  the  function  of  the  thyroid  gland  is  abol- 
ished and  to  assume  vicariously  the  duties  of  that  organ.  In  how 
far  this  points  to  a  normal  similarity  in  function  of  the  two  organs 
must,  at  present,  be  left  undetermined.  In  cases  of  enlargement 
of  the  pituitary  body  profound  changes  in  nutrition,  characterized 
chiefly  by  overgrowth,  frequently  take  place  in  the  bones  of  the 
skeleton  (acromegaly). 

The  nervous  supply  of  the  anterior  lobe  consists  of  non-medul- 

FIG.  167. 


Section  from  the  glandular  lobe  of  the  hypophysis;  child  six  months  old.  (Lothringer.) 
The  close  relations  between  the  epithelial  cells  and  the  capillary  bloodvessels,  and  the 
differences  in  the  cells,  are  indicated  in  this  figure.  The  red  blood-corpuscles  within  the 
capillaries  have  been  stained  dark. 

lated  fibres,  destitute  of  ganglion-cells,  which  ramify  about  the 
vessels  and  send  some  of  their  terminal  twigs  between  the  epithelial 
cells. 

The  posterior  lobe  consists  of  tissues  resembling  those  of  the 
central  nervous  system  :  ganglion-cells,  non-medullated  fibrils,  and 
neuroglia-cells.  Within  its  substance  there  are  also  peculiar  oval 
bodies  surrounded  by  nervous  terminations,  to  which  sensory  func- 
tions have  been  attributed,  and  small  follicles,  lined  with  cubical 
epithelium. 


192 


NORMAL  HISTOLOGY. 


5.  The  Thymus. — This  organ  reaches  its  fullest  development  at 
about  the  second  year  of  life,  after  which  retrograde  changes,  end- 
ing in  the  substitution  of  fibrous  and  adipose  tissues  for  its  proper 
structure,  take  place.  Its  development  begins  as  an  ingrowth  of 
epithelium  from  the  branchial  clefts.  This  epithelium  forms  a 


FIG.  168. 


Two  concentric  corpuscles  of  Hassall,  from  the  foetal  thymus.    (Klein.) 

branching,  solid  column  of  cells  surrounded  by  embryonic  connec- 
tive tissue,  which  develops  into  lymphadenoid  tissue.  In  the 
meantime  the  epithelial  strands  are  broken  up  and  the  whole  organ 
becomes  converted  into  a  structure  resembling  a  collection  of  lymph- 
follicles,  but  with  this  difference  :  that  remnants  of  the  epithelial 
strands  remain  in  the  centres  of  many  of  the  follicles,  where  their 


FIG.  169. 


Lobule  from  the  thymus  of  a  child.  (Schiiffer.)  tr,  trabecula;  a,  nodule  of  denser  lymph- 
adenoid  tissue  at  periphery  ("cortex");  b,  b,  sections  of  vessels  within  the  less  dense 
lymphadenoid  tissue  in  the  centre  ("medulla ") ;  c,  c,  concentric  corpuscles  of  Hassall. 

cells  become   flattened   and   imbricated.     These   epithelial  masses 
are  known  as  the  concentric  corpuscles  of  Hassall  (Fig.  168). 

The  thymus  is  enclosed  in  a  fibrous  capsule,  which  penetrates  its 
substance,  dividing  it  into  lobes  and  lobules.  Each  of  these  lobules 
closely  resembles  a  lymph-follicle,  but  it  is  doubtful  whether  lymph- 


THE  DUCTLESS  GLANDS.  193 

sinuses,  corresponding  to  those  in  the  lymphatic  nodes,  are  present 
in  the  thymus  (Fig.  169). 

The  function  of  the  thymus  is  still  a  matter  of  doubt.  It  has 
been  regarded  as  one  of  the  sites  in  which  red  blood-corpuscles  are 
formed,  and  also  as  a  temporary  lymphadenoid  organ  playing  the 
part  of  the  lymph-nodes  until  these  have  become  fully  developed  in 
other  parts  of  the  body. 

The  thymus  is  connected  with  the  thyroid  by  a  strand  of  thymus- 
tissue,  and  isolated  thymus-lobules  are  found  embedded  in  the 
edges  of  the  thyroid,  near  the  parathyroid  body  (see  Fig.  159). 

The  bloodvessels  ramify  in  the  septa  of  the  organ  and  send 
branches  into  the  lymphoid  follicles.  The  lymphatic  vessels  accom- 
pany the  bloodvessels  and  surround  the  lobules,  but  do  not  appear 

FIG.  170. 

I 


/     ''<•* 

:^   V    ~  V;,        V 


: 


-<©*•-     ^          OF 

^  ? 


<e  -s. 

Section  of  the  carotid  gland  and  carotid  arteries  near  their  origin.  (Marchand.)  ci,  internal 
carotid ;  ce,  external  carotid ;  glc,  carotid  gland ;  I,  I,  groups  of  epithelial  cells ;  i,  fibrous 
tissue  between  the  epithelial  groups ;  g,  bloodvessel.  Numerous  vessels  are  also  seen 
within  the  gland. 

to  penetrate  into  the  lymphadenoid  tissue.  The  nerves  are  small 
and  not  numerous.  They  accompany  the  bloodvessels,  but  nervous 
terminations  have  not  been  traced  as  distributed  to  the  lymphade- 
noid tissue. 

The  involution  of  the  gland  appears  to  be  accomplished  through 

13 


194 


NORMAL  HISTOLOGY. 
FIG.  171. 


Portion  of  the  same  gland  as  Fig.  170,  more  highly  magnified :  p,  epithelial  cells ;  g,  capillary 
bloodvessels ;  e,  endothelium  forming  the  capillary  wall. 

a  proliferation  of  the  fibrous  tissue  around  the  lobules,  which  en- 
croaches upon  the  lymphadenoid  tissue  and  gradually  replaces  it. 
This  fibrous  tissue  subsequently  becomes,  in  great  measure,  con- 
verted into  adipose  tissue.  It  appears  as  though  the  endothelium 
of  the  bloodvessels  also  proliferated,  giving  rise  to  masses  of  imbri- 

FIG.  172. 


Section  of  the  coccygeal  gland.    (Sertoli.)     The  group  of  cells,  apparently  of  epithelial 
nature,  is  traversed  by  small  bloodvessels  and  enclosed  by  fibrous  tissue. 

cated  cells  within  the  follicles  and  leading  to  an  obliteration  of  the 
vascular  lumen. 

6.  The  Carotid  Glands. — These  consist  of  groups  or  islets  of  epithe- 
lial cells,  surrounded  by  fibrous  tissue  from  which  numerous  capil- 


THE  DUCTLESS  GLANDS.  195 

lary  bloodvessels  are  distributed  in  close  relation  with  the  epithelial 
cells  (Figs.  170  and  171).     Their  function  is  unknown. 

7.  The  Coccygeal  Gland. — This  body  is  made  up  of  groups  and 
strands  of  cells,  probably  of  epithelial  nature,  closely  applied  to  the 
walls  of  capillary  bloodvessels  and  surrounded  by  fibrous  tissue. 
Its  function  and  mode  of  origin  are  both  unknown  (Fig.  172). 


CHAPTER  XVI. 
THE  SKIN. 

THE  skin  consists  of  a  deeper,  fibrous  portion,  the  corium,  or  true 
skin,  and  a  superficial,  epithelial  layer,  the  epidermis.  As  a  part 
of  the  latter,  and  developing  from  it,  the  skin  contains  two  sorts 
of  glands,  the  sebaceous  and  the  sweat-glands,  and  two  kinds  of 
appendages,  the  hairs  and  nails. 

The  corium  is  composed  of  vascularized  fibrous  tissue,  which  is 

FIG.  173. 


Section  of  skin  perpendicular  to  the  surface.  (Arloing.)  a,  horny  layer  of  the  epidermis  ; 
b,  rete  mucosum ;  c,  surface  of  the  corium  ;  d,  sebaceous  gland ;  e,  areolar  tissue  of  the 
corium;  /,  hair-shaft  -within  the  hair-follicle;  g,  lobule  of  adipose  tissue  in  the  subcu- 
taneous tissue;  h,  sweat-gland ;  mh,  arrector  pili ;  p,  papilla  of  the  corium  extending  into 
the  rete  mucosum.  The  lower  limit  of  the  corium  is  not  marked  by  a  plane  parallel  to 
that  of  the  surface  of  the  skin.  The  corium  may  be  said  to  end  where  the  fat  of  the  sub- 
cutaneous tissue  begins. 

made  up  of  bundles  loosely  arranged  in  its  deeper  portions,  where  it 
becomes  continuous  with  the  subcutaneous  areolar  tissue,  and  contains 

196 


THE  SKIN.  197 

a  variable  amount  of  fat,  but  more  compactly  disposed  in  the  super- 
ficial portions,  where  it  comes  in  contact  with  the  epidermis,  into 
which  it  projects  in  the  form  of  papillae.  Some  of  these  papillae 
contain  loops  of  capillary  bloodvessels,  while  others  are  occupied 
in  their  centres  by  peculiar  nerve-endings,  called  "  tactile  corpus- 
cles." In  some  situations,  notably  upon  the  palms  and  soles,  the 
papillae  of  the  corium  are  arranged  in  rows.  In  most  parts  of  the 
skin  they  are  irregularly  scattered  over  the  surface  of  the  corium 
(Fig.  173). 

The  epidermis  (Fig.  174)  is  a  layer  of  stratified  epithelium  in 


FIG.  174. 


Vertical  section  of  the  epidermis  of  the  finger.  (Ranvier.)  a,  stratum  corneum,  or  horny 
layer ;  b,  stratum  lucidum  ;  c,  stratum  granulosum ;  d,  rete  mucosum  ;  e,  "  prickles  "  on 
the  cells  bordering  on  the  corium,  which  is  not  represented. 

which  the  cells  multiply,  where  they  are  situated  near  the  corium, 
and  gradually  suffer  a  conversion  into  horny  scales  as  they  are 
pushed  toward  the  surface,  where  they  are  eventually  desquamated. 
The  changes  the  cells  undergo  in  their  journey  from  the  deeper 
layers  of  the  epidermis  to  its  surface  cause  variations  in  their 
appearances  which  have  occasioned  a  division  of  the  epidermis  into 
a  number  of  more  or  less  well-defined  strata.  The  deepest  stratum, 
where  the  cells  multiply  and  grow,  is  called  the  "  rete  mucosum." 
It  is  composed  of  cells  which  gradually  enlarge,  becoming  rich  in 
cytoplasm,  and  are  connected  with  each  other  by  minute  cytoplas- 
mic  "  prickles,"  between  which  there  is  a  space  affording  a  channel 
for  the  circulation  of  nutrient  fluids  (Fig.  39).  Above  the  rete 
mucosum  the  cells  appear  more  granular,  owing  to  the  formation 


198  NORMAL  HISTOLOGY. 

of  a  substance,  called  "eleidin,"  within  the  cytoplasm  (Fig.  175). 
These  cells  form  the  "  stratum  granulosum."  The  eleidin  appears 
to  be  produced  at  the  expense  of  the  cytoplasm,  the  process  being 
a  form  of  degeneration,  so  that  after  a  while  the  whole  cell  is  con- 
verted into  a  homogeneous  material  in  which  the  nucleus  persists 
in  a  form  deprived  of  chromatin,  and  therefore  insusceptible  of 
staining.  The  presence  of  these  cells  gives  rise  to  the  formation  of 
the  "stratum  lucidum"  immediately  above  the  stratum  granules  urn. 
Within  this  stratum  the  eleidin  appears  to  pass  into  a  closely  related 
substance  of  a  horny  nature,  keratin,  and  the  cells  become  con- 

FIG.  175. 


Cell  from  the  stratum  granulosum  of  the  epidermis  of  the  scalp.  (Rabl.)  The  cytoplasm  of 
the  cell  has  been  in  great  measure  converted  into  granules  of  eleidin ;  the  chromatin  of 
the  nucleus  has  retracted  into  a  compact  mass  in  the  centre  of  the  nuclear  region,  and  is 
destined  to  disappear.  This  cell  is  from  a  section  made  parallel  to  the  surface  of  the 
epidermis,  which  accounts  for  its  shape  and  apparent  size. 

verted  into  firmly  compacted  scales,  which  make  up  the  most  super- 
ficial or  horny  layer  of  the  epidermis. 

The  sweat-glands  are  simple  tubular  glands,  the  deep  ends  of 
which  are  irregularly  coiled  to  form  a  globular  mass  situated  in 
the  deeper  portion  of  the  corium  or  at  various  depths  in  the  sub- 
cutaneous tissue.  From  these  coils  the  excretory  duct  passes 
through  the  corium  to  the  epidermis,  where  it  opens  into  a  spiral 
channel  between  the  epidermal  cells,  ending  in  an  orifice  at  the  sur- 
face of  the  skin. 

The  epithelial  lining  of  the  sweat-gland  is  a  continuation  of  the 
stratum  mucosum,  from  which  it  is  derived,  and  consists  of  two  or 
more  layers  of  cubical  cells  in  the  duct  and  of  a  single  layer  of  more 
columnar  cells  in  the  deeper,  secreting  portion  of  the  gland.  In 
the  duct  these  cells  rest  upon  a  homogeneous  basement-membrane, 
but  in  the  secreting  portion  there  is  a  more  or  less  complete  layer 
of  elongated  cells,  similar  in  appearance  to  those  of  smooth  muscular 
tissue,  which  lie  between  the  epithelial  cells  and  the  basement-mem- 
brane (Fig.  176).  It  is  doubtful  whether  these  are  really  muscle- 
cells.  The  loops  of  the  glandular  coil  are  surrounded  by  fibrous 
tissue,  which  contains  the  bloodvessels  supplied  to  the  gland  and 
serves  to  support  it  in  its  globular  form. 


THE  SKIS.  199 

The  sebaceous  glands  can  best  be  described  in  connection  with 
the  hairs  and  their  follicles. 

The  bulbous  attachment,  or  "  root,"  of  the  hair,  and  the  adjacent 
portion  of  its  shaft,  are  contained  in  an  invagination  of  the  corium 
and  epidermis, called  the  "hair-follicle"  (Fig.  173,/).  This  is  sur- 
rounded by  fibrous  tissue,  forming  its  external  coat,  which  may  be 
imperfectly  distinguished  into  an  outer  layer,  containing  relatively 
abundant  longitudinal  fibres,  and  an  inner  layer,  in  which  encircling 

FIG.  176. 
,a 


Section  through  the  coiled  end  of  a  sweat-gland.  (Klein.)  a,  &,  duct  in  longitudinal  and 
cross-section ;  c,  d,  sections  of  the  secretory  portion  of  the  tubule.  Above  d  is  a  little  adi- 
pose tissue.  The  rest  of  the  section  is  composed  of  vascularized  areolar  tissue. 

fibres  predominate.  At  the  bottom  of  the  follicle  this  fibrous  tissue 
becomes  continuous  with  that  of  a  vascularized  papilla,  similar  to 
those  existing  on  the  surface  of  the  corium,  which  projects  into  the 
root  of  the  hair. 

The  fibrous  sac  constituting  the  outer  part  of  the  hair-follicle  is 
lined  with  a  continuation  of  the  epidermis,  leaving  a  cylindrical 
cavity  occupied  by  the  hair.  This  layer  of  epithelium  is  reflected 
upon  the  surface  of  the  papilla,  where  it  forms  the  root  of  the  hair, 
and  then  passes  into  the  shaft,  which  is  made  up  of  cells,  derived 
from  those  of  the  root,  that  have  suffered  keratoid  degeneration. 

The  epithelium  lining  the  follicle,  as  well  as  that  which  composes 
the  hair,  is  not  of  uniform  character  throughout,  and  has  been  divided 
into  a  number  of  layers,  to  which  different  observers  have  given 
special  names.  The  group  of  cells  surrounding  the  papilla  are  the 
seat  of  the  multiplication  which  results  in  the  growth  of  the  hair. 
Upon  the  surface  of  the  shaft  these  cells  become  transformed  into 


200  NORMAL  HISTOLOGY. 

thin  scales,  each  of  which  overlaps  that  above  it.     This  very  thin 

FIG.  177. 


7.. 

— I 


Hair-follicle  from  the  human  scalp.  (Mertsching.)  Longitudinal  axial  section  through  the 
fundus :  a,  b,  longitudinal  and  encircling  layers  of  the  fibrous  coat ;  c,  hyaline  layer, 
formed  of  an  outer  faintly  fibrillated  and  an  inner  more  homogeneous  lamina ;  d, 
papilla ;  e,  outer  root-sheath,  continuous  with  rete  mucosum  of  epidermis ;  ef,  its  outer 
layer,  continuous  with  deepest  cells  of  rete  and  with  columnar  cells  covering  the  papilla ; 
e",  its  inner  layer,  continuous  with  the  cortical  cells  of  hair ;  /,  Henle's  sheath  ;  g,  Hux- 
ley's layer ;  h,  cuticle  of  root-sheath  ;  k,  cuticle  of  hair ;  I,  cortical  cells  of  the  hair ;  m, 
medulla. 

layer  is  called  the  "  cuticle  "  of  the  hair.     Beneath  the  cuticle  the 
cells  are  crowded  together  into  fusiform  or  fibrous  elements,  which 


THE  SKIN.  201 

make  up  the  chief  mass  of  the  hair-shaft.  In  the  centre  of  this 
mass  there  is  sometimes  a  line  of  more  loosely  aggregated  cells, 
forming  the  "  medulla  "  of  the  hair.  When  this  is  present  the  sur- 
rounding part  of  the  shaft,  between  it  and  the  cuticle,  is  known  as 
the  "cortex"  (Figs.  177  and  178). 

The  sebaceous  glands  (Fig.  173,  d)  are  sacculations  in  the  corium 
near  the  hair-follicles,  which  are  filled  with  epithelial  cells.  The 
cells  at  the  periphery  divide,  and,  as  they  increase  in  size,  push 

FIG.  178. 


Hair-follicle  from  the  human  scalp.  (Mertsching.)  Cross-section  from  middle  third  of 
the  follicle:  6,  longitudinal  and  encircling  layers  of  the  fibrous  coat;  c,  hyaline  layer, 
formed  of  an  outer  faintly  fibrillated  and  an  inner  more  homogeneous  lamina,  d ;  e,  outer 
root-sheath,  continuous  with  rete  mucosum  of  epidermis  ;/,  Henle's  sheath;  g,  Huxley's 
layer;  h,  cuticle  of  root-sheath;  k,  cuticle  of  hair;  I,  cortical  cells  of  the  hair;  ra, 
medulla. 

each  other  toward  the  centres  of  the  sacs.  Here  they  undergo  a 
fatty  degeneration,  ending  in  destruction  of  the  cells  and  the  forma- 
tion of  an  oily  secretion,  the  sebum,  which  is  discharged  into  the 
hair-follicle  a  short  distance  below  its  opening  on  the  surface  of  the 
skin.  The  sebum  is  a  lubricant  for  both  the  hair  and  the  epi- 
dermis (Fig.  179). 

The  color  of  the  epidermis  and  of  the  hair  is  due  to  a  pigmenta- 
tion of  the  cells  in  the  deeper  layers  of  the  rete  mucosum  and  those 
composing  the  hair.  The  whiteness  of  the  hair  which  comes  with 
years  is  due  to  little  spaces  which  appear  in  unusual  numbers 
between  the  cells  of  the  cortex,  and  are  filled  with  air,  reflecting  the 
light  and  masking  the  pigmentation  of  the  cells. 

The  nails  are  especially  thick  and  condensed  masses  of  epithelial 
cells  which  have  undergone  keratoid  degeneration  and  are  closely 
compacted.  They  are  produced  at  the  root  of  the  nail,  and  as  they 


202 


NORMAL  HISTOLOGY. 


H 


Sebaceous  gland  from  the  external  auditory  canal.  (Benda  and  Guenther's  Atlas. )  a,  epi- 
thelium continuous  with  that  lining  the  hair-follicle ;  b,  layer  of  proliferating  epithelium 
lining  the  sac  of  the  gland ;  c,  enlarged  cell  beginning  to  undergo  fatty  metamorphosis 
of  the  cytoplasm  ;  d,  mass  of  sebum  derived  from  a  single  epithelial  cell. 

accumulate  push  the  body  of  the  nail  forward.     They,  therefore, 

FIG.  180. 


Section  through  the  root  of  the  nail  of  a  sixth-months  foetus.  (Ernst.)  a,  matrix  of  the  nail 
formed  by  an  invagination  of  the  rete  mucosum.  Near  the  point  indicated  by  the  letter 
the  epithelial  cells  have  begun  to  change  into  keratoid  material.  6,  loosened  scales  of  the 
surface  of  the  nail ;  c,  remains  of  the  foetal  cuticle  which  have  not  become  keratoid. 
The  letter  a  and  line  proceeding  from  it  both  lie  in  the  corium. 

correspond  to  the  horny  layer  of  the  epidermis,  which  has  become 
modified  to  form  these  special  structures  (Fig.  180). 


THE  SKIN.  203 

The  skin  contains  little  muscular  bands,  the  arrectores  pili  (Fig. 
173,  mh\  composed  of  smooth  muscular  fibres,  which  are  attached 
to  the  fibrous  coat  of  the  hair-follicles  near  their  deep  extremities 
and  to  the  superficial  layer  of  the  corium  on  the  side  of  the  fol- 
licle toward  which  the  hair  leans.  The  action  of  these  mus- 
cles is  to  cause  the  hair  to  assume  a  more  vertical  position,  and 
to  raise  it  and  the  follicle,  producing  the  effect  known  as  "  goose 
flesh."  By  their  contraction  they  may  also  aid  in  the  discharge 
of  sebum,  since  their  fibres  often  partially  invest  the  sebaceous 
glands. 

The  functions  of  the  skin  have  reference  to  its  being  the  organ 
coming  in  contact  with  the  external  world.  The  epidermis  protects 
the  underlying  tissues  from  mechanical  and  chemical  injury  and 
from  desiccation.  The  keratin  in  its  horny  layer  forms  an  imper- 
vious and  tough  investment  of  the  body,  which  is  highly  resistant 
toward  chemical  action  and  mechanical  abrasion,  and  is  constantly 
renewed  from  the  layers  that  lie  beneath  it.  It  is  kept  in  a  pliable 
condition  by  the  sebum  discharged  upon  its  surface  and  by  the 
moisture  proceeding  from  the  sweat-glands,  the  "  insensible  perspi- 
ration." The  skin  also  plays  a  prominent  role  in  the  regulation  of 
the  bodily  temperature.  When  its  vessels  are  contracted  the  amount 
of  heat  given  off  from  the  surface  of  the  body  is  reduced ;  when 
they  are  dilated,  it  is  increased.  A  further  loss  of  heat  is  occa- 
sioned by  an  increased  secretion  of  sweat,  which  bathes  the  surface 
of  the  skin  and  abstracts  from  the  body  the  heat  required  to  con- 
vert it  into  vapor.  Under  the  influence  of  sudden  and  marked 
cold  the  vessels  of  the  skin  become  much  contracted  and  the 
arrectores  pili  shorten,  occasioning  the  production  of  a  roughness 
of  the  skin,  goose-flesh,  and  probably  also  a  discharge  of  se- 
bum, which  reduce  the  evaporation  from  the  skin.  At  the  same 
time  a  reflex  rhythmical  contraction  and  relaxation  of  the  volun- 
tary muscles  is  brought  about — shivering,  which  increases  the 
liberation  of  stored  energy  within  the  body,  and  causes  it  to  appear 
as  heat.  In  conjunction  with  these  functions  the  skin  is  also  an 
organ  of  tactile  and  thermal  sensation,  functions  which  are  not 
merely  beneficial  in  themselves,  but  are  useful  auxiliaries  in  the 
furthering  of  the  other  functions  exercised  by  the  skin.  It  is  a 
common  experience  that  the  sensation  of  cold  stimulates  the  desire 
for  muscular  exercise,  of  which  the  liberation  of  heat  is  a  result. 
The  sensation  of  pain  often  gives  timely  warning  of  exposure  to  an 


204 


NORMAL  HISTOLOGY. 


injury  sufficiently  great  to  overcome  the  usual  protective  powers  of 
the  epidermis.  Thus  we  see  that  when  the  automatic  action  of  the 
skin  is  inadequate  for  the  performance  of  its  functions  it  calls  forth 


FIG.  181. 


Hair-rudiment  from  an  embryo  of  six  weeks.  (Kolliker.)  a,  horny  layer  of  epidermis  ;  6, 
Malpighian  layer,  rete  mucosum  ;  i,  limiting  membrane  ;  m,  m,  cells  extending  from  the 
rete  mucosum  to  fill  the  future  hair-follicles.  The  elongated  cells  near  the  base  of  the 
sac  are  those  from  which  hair  is  developed.  The  secreting  glands  of  the  body  arise  from 
some  epithelial  layer  in  a  similar  manner. 

an  auxiliary  activity  of  other  organs,  through  the  medium  of  the 
nervous  system. 

The  hair-follicles  are  developed  from  the  rete  mucosum  of  the  epi- 
dermis, and  first  appear  as  little  masses  of  cells  growing  into  the 

FIG.  182. 


ms8££3&SS$$wm    d 


Section  of  developing  tooth.  From  embryo  of  sheep.  (Bohm  and  Davidoff.)  a,  epi- 
thelium of  the  gum ;  b,  its  deepest  layer ;  c,  superficial  cells  of  the  enamel-pulp ;  d, 
enamel-pulp  formed  of  modified  epithelial  cells ;  s,  cells  of  the  enamel-pulp  destined  to 
produce  the  enamel  ("  adamantoblasts  ") ;  p,  dental  papilla. 

underlying  connective  tissues  (Fig.   181).     The  sebaceous  glands 
arise  as  oifshoots  from  these  cellular  masses. 


THE  SKIN. 


205 


The  Teeth. — The  development  of  the  teeth  presents  close  anal- 
ogies to  that  of  the  hairs.  They  also  first  appear  as  little  masses 
of  cells,  growing  into  the  connective  tissues  of  the  alveolar  proc- 
esses from  the  stratified  epithelium  covering  them.  Into  the  bases 
of  these  masses  connective-tissue  papillae  are  developed,  which 
eventually  become  differentiated  into  the  pulp  of  the  tooth-cavities. 
The  epithelial  cells  which  immediately  surround  these  papillae  be- 
come elongated  to  a  columnar  form  and  then  become  converted 

FIG.  183. 


Y 


Section  of  developing  tooth.  From  embryo  of  rabbit.  (Freuiid.)  ep,  epithelium  of  gum; 
a/i,  epithelial  cells  forming  outer  layer  of  the  enamel-pulp  of  the  temporary  tooth ;  L,  sim- 
ilar layer  belonging  to  the  rudiment  of  the  permanent  tooth ;  &r,  enamel-pulp ;  p,  dental 
pulp  of  the  tooth-cavity ;  d,  dentin;  v,  bloodvessels;  B,  rudiment  of  second  or  permanent 
tooth ;  a,  embryonic  connective  tissue  of  the  alveolar  process. 

into  or  elaborate  the  tissue  of  the  enamel.  The  superficial  cells 
of  the  papillae  likewise  elongate  and  produce  the  dentin.  The 
cement  which  constitutes  the  outer  layer  of  the  root  of  the  tooth 
is  bone,  and  is  developed  from  the  foetal  connective  tissue  in  that 
region  (Figs.  182  and  183). 

Only  a  brief  description  of  the  structures  entering  into  the  forma- 
tion of  the  fully  developed  tooth  can  be  given  here.  For  a  more 
detailed  account  of  them  the  student  is  referred  to  special  works  on 
the  subject. 


206 


NORMAL  HISTOLOGY. 


FIG.  184. 


The  centre  of  the  tooth  is  hollow,  and  the  cavity  opens  by  a 
small  orifice  at  the  tip  of  the  root.     This  cavity  is  filled  with  a 

highly  vascular  delicate  areolar  tissue, 
richly  supplied  with  nerves.  Where 
this  pulp  is  in  contact  with  the  tooth 
its  outer  layer  is  made  up  of  modified 
connective-tissue  cells,  odontoblasts, 
which  are  capable  of  elaborating  den- 
tin.  The  body  of  the  tooth  is  com- 
posed of  dentin.  This  contains  minute 
canals,  analogous  to  the  canaliculi  in 
bone,  but  much  longer.  They  extend 
from  the  pulp-cavity  nearly,  if  not  quite, 
to  the  outer  boundary  of  the  dentin, 
and,  toward  their  terminations,  give  off 
branches.  These  canals  are  occupied 
by  long  fibrous  processes  of  the  odonto- 
blasts already  mentioned. 

The  crown  of  the  tooth,  down  to  its 
neck,  is  covered  with  enamel.  This 
is  a  tissue  derived  from  epithelium, 
and  is  composed  of  long,  prismatic  ele- 
ments extending  from  the  surface  of 
the  tooth  to  the  dentin.  These  prisms 
have  a  polygonal  cross-section  and  are 
held  together  by  a  hard  cement-sub- 
Thev  are  not  perfectly  recti- 

. 

linear,  but  pursue  a  wavy  course,  being 
disposed  in  laminae  or  bundles,  in  which 

the  prisms  have  not  quite  the  same  direction. 

The  root  of  the  tooth,  below  the  point  where  the  enamel  ends,  is 

covered  with  cement,  which  has  the  structure  of  ordinary  bone,  but 

is  usually  devoid  of  Haversian  canals  (Fig.  184). 


section  of  a  human  tooth   stance. 

having  but  one  root  :  a,  enamel  ; 

6,  dentin;  c,  cement. 


CHAPTER  XVII. 

THE  REPRODUCTIVE  ORGANS. 

I.  IN  THE  FEMALE. 

THE  female  reproductive  organs  are :  (1)  the  ovary,  in  which  the 
egg  is  produced  ;  (2)  the  Fallopian  tube,  through  which  it  is  con- 
veyed to  (3)  the  uterus,  where  it  develops  into  the  foetus,  and  from 
which  the  child  at  maturity  passes  through  (4)  the  vagina  and  (5) 
external  genitals  into  the  external  world. 

1.  The  Ovary  (Fig.  185). — The  free  surface  of  the  ovary  is  cov- 
ered with  a  single  layer  of  columnar  epithelium,  called  the  "germinal 
epithelium."  Beneath  this  the  substance  of  the  organ  is  composed 
of  a  vascularized  fibrous  tissue,  the  "  stroma,"  which  is  slightly  dif- 
ferent in  the  details  of  its  structure  in  different  parts  of  the  organ. 
Immediately  beneath  the  germinal  epithelium  it  is  slightly  richer 
in  intercellular  substance  than  in  the  subjacent  parts,  so  that  the 
organ  appears  to  have  a  proper  fibrous  coat.  This  coat  is  not  dis- 
tinct, however,  and  gradually  passes  into  a  highly  cellular  form  of 
fibrous  tissue,  in  which  the  spindle-shaped  cells  are  separated  by 
only  a  small  amount  of  a  delicate  fibrous  intercellular  substance. 
Toward  the  hilum  of  the  ovary  this  connective  tissue  passes  into  a 
more  distinctly  fibrous  tissue,  containing  a  larger  amount  of  inter- 
cellular substance  and  cells  that  are  less  prominent.  In  this  portion 
of  the  stroma  the  larger  vessels  supplying  the  organ  are  situated, 
and  from  it  they  send  smaller  branches  throughout  the  stroma  of 
the  organ.  Within  the  more  cellular  regions  of  the  stroma  are  the 
structures  known  as  the  Graafian  follicles,  each  of  which  contains 
an  ovum.  In  order  to  understand  the  structure  of  these  Graafian 
follicles  it  will  be  well  to  trace  the  history  of  their  development. 

The  Graafian  follicles  and  ova  are  derived  during  foetal  life  from 
the  germinal  epithelium  covering  the  ovary.  From  this  layer  of 
cells  little  columns  of  epithelium  make  their  way  into  the  stroma, 
where  they  become  broken  up  into  small  isolated  groups,  in  each  of 
which  one  of  the  cells  develops  into  an  ovum,  while  the  rest  con- 
tribute to  the  formation  of  the  Graafian  follicle.  This  mode  of  origin 

207 


208 


NORMAL  HISTOLOGY. 


may  serve  to  explain  the  fact  that  the  younger  Graafian  follicles 
are  most  abundant  in  the  peripheral  portion  of  the  stroma.  At 
first  the  Graafian  follicle  consists  of  a  large  central  cell,  the  ovum, 


FIG.  185. 


Section  from  the  ovary  of  an  adult  bitch.  (Waldeyer.)  a,  germinal  epithelium ;  b,  b,  columns 
of  germinal  epithelium  within  the  stroma ;  c,  c,  small  follicles ;  d,  much  more  advanced 
follicle ;  e,  discus  proligerus  and  ovum ;  /,  second  ovum  in  same  follicle  (a  rare  occur- 
rence) ;  g,  fibrous  coat  of  the  follicle ;  h,  basement-membrane ;  i,  membrana  granulosa 
of  epithelium;  d,  liquor  folliculi;  k,  old  follicle  from  which  the  ovum  has  been  dis- 
charged ;  I,  bloodvessels ;  m,  m,  sections  of  the  parovarium ;  y,  ingrowth  from  the  ger- 
minal epithelium ;  z,  transition  from  the  germinal  epithelium  to  the  peritoneal  endo- 
thelium. 

surrounded  by  an  envelope  of  somewhat  flattened  epithelial  cells, 
which  are  in  direct  contact  externally  with  the  unmodified,  highly 
cellular  tissue  of  the  stroma  (Fig.  186). 

As  the  Graafian  follicle  develops,  its  position  in  the  ovary  becomes 
more  central,  and  the  cells  around  the  ovum  lose  their  flattened 
shape  and  divide,  forming  a  double  layer  of  cubical  or  columnar 
cells.  These  two  layers  then  become  separated  by  a  clear  fluid,. 


THE  REPRODUCTIVE  ORGANS.  209 

the  liquor  folliculi,  so  that  the  outer  layer  forma  the  wall  of  a  sac, 
while  the  inner  layer  remains  as  a  close  investment  of  the  ovum. 
The  cells  of  these  two  layers  multiply :  those  surrounding  the 
ovum  forming  the  "  discus  proligertis,"  and  those  lining  the  sac  the 
"  tunica  granulosa  "  ;  hut  they  blend  with  each  other  at  one  point  on 
the  wall  of  the  follicle,  so  that  the  ovum  retains  a  fixed  position. 
Meanwhile  the  tissue  of  the  stroma  undergoes  modifications  which 


FIG.  186. 


Graaflan  follicle  and  stroma  in  ovary  of  adult  sow.  (Plato.)  The  ovum  occupies  the  centre 
of  the  follicle,  appearing  as  a  very  large  cell  with  a  large  vesicular  nucleus  ("germinal 
vesicle"),  within  which  is  a  large  nucleolus  ("germinal  spot"),  exceeding  in  size  the 
whole  nucleus  of  the  surrounding  epithelial  cells  of  the  follicle.  The  cells  of  the  stroma 
are  arranged  about  the  follicle  as  though  to  form  the  fibrous  coat  of  the  latter.  In  the 
lower  portion  of  the  figure  are  three  large  cytoplasmic  cells,  containing  globules  of  fat 
and  granules  of  pigment.  These  cells  are  analogous  to  those  found  in  the  interstitial 
tissue  of  the  testis.  The  epithelium  of  the  Graafian  follicle,  and  the  ovum,  also  contain 
globules  of  fat  of  various  sizes,  stained  black  by  the  osmic  acid  used  in  the  preparation 
of  the  specimen. 

contribute  a  clear  basement-membrane  and  a  fibrous  envelope,  the 
"  membrana  propria,"  to  the  structure  of  the  follicle. 

The  follicle  now  enlarges,  as  the  result  of  an  increase  in  the 
amount  of  the  liquor  folliculi,  eventually  approaches  the  surface  of 
the  ovary  at  some  point,  and  then  ruptures,  discharging  the  ovum. 

After  the  rupture  of  the  Graafian  follicle  and  the  escape  of 
its  contents  a  slight  hemorrhage  usually  takes  place  into  its 
cavity,  which  then  appears  filled  with  remains  of  the  liquor  fol- 
liculi mixed  with  coagulated  blood.  Into  this,  granulations1  now 

1  See  Chapter  XXIV. 
14 


210  NORMAL  HISTOLOGY. 

develop  from  the  fibrous  wall,  replacing  the  clot  and  eventually 
producing  a  scar.  This  process  is  much  more  rapid  in  case  the 
ovum  is  not  impregnated  (corpus  hsemorrhagicum)  than  when  im- 
pregnation has  taken  place.  In  the  latter  case  the  productive 
inflammation  is  more  marked,  and  is  accompanied  by  a  fatty 
degeneration  of  the  older  granulations  Avhich  gives  them  a  yel- 
lowish tinge  (corpus  luteum).  In  the  centre  of  this  yellowish  zone 
is  the  remainder  of  the  clot,  and  about  its  periphery  an  envelope  of 
fibrous  tissue,  which  is  usually  irregular  in  contour.  The  corpus 
luteum  finally  becomes  a  mass  of  cicatricial  tissue  of  greater  size 
than  that  resulting  from  a  corpus  haBmorrhagicum  (corpus  album) 
(Figs.  187  and  188). 

FIG.  187. 

«- 


^'f.^vAvS^oS**^**  -A 

?^&&\V££'  *'*' 


x  ' ke 

"-,-,:       ; 

f 

thi  e 

Section  from  rabbit's  ovary,  illustrating  the  formation  of  the  corpus  luteum.  (Sobotta.) 
Recently  ruptured  Graafian  follicle,  ke,  germinal  epithelium;  beneath  it,  the  ovarian 
stroma.  Bounding  the  follicle  externally  is  the  fibrous  capsule  of  the  follicle.  Within 
this,  thi,  is  a  layer  of  proliferating  fibrous  tissue,  composed  of  polyhedral  cells  with  round 
nuclei.  Among  these  are  elongated  nuclei  belonging  to  endothelial  cells  springing  from 
the  capillaries,  and  destined  to  form  the  walls  of  future  bloodvessels ;  e,  epithelium  of 
the  membrana  granulosa.  Within  this  are  the  viscid  remains  of  the  liquor  folliculi, 
containing  a  few  red  blood-corpuscles  and  some  epithelial  cells  detached  from  the  mem- 
brana granulosa,  bl,  red  blood-corpuscles.  This  section  was  prepared  from  an  ovary 
about  twenty-four  hours  after  coitus,  and  the  development  of  the  layer  thi  probably 
took  place  within  that  time. 

2.  The  Fallopian  Tube. — The  free  surface  of  the  Fallopian  tube 
is  covered  by  a  serous  membrane,  continuous  with  the  rest  of  the 
peritoneum.  This  rests  upon  fibrous  tissue,  in  which  the  longi- 
tudinal bundles  of  smooth  muscular  tissue  constituting  the  external 


THE  REPRODUCTIVE  ORGANS.  211 

FIG.  188. 


fv>-  «    ••?-»"•     '^     *'~\ 
- 

. 


Section  of  young  corpus  lutcum,  four  days  after  coitus.  The  proliferating  connective  tissue 
has  nearly  filled  the  cavity  of  the  follicle,  only  a  small  mass  of  fibrin  remaining  in  its 
centre.  The  young  connective  tissue  is  highly  vascularized,  the  blood  in  some  of  the 
capillaries  being  represented,  g.  ke,  germinal  epithelium.  Below  is  the  margin  of  a 
Graafian  follicle,  with  its  membrana  granulosa. 

muscular  coat  are  situated.  This  is  followed  by  an  internal  mus- 
cular coat  of  encircling  bundles  of  smooth  muscular  tissue,  inside 
of  which  is  the  submucous  coat  of  areolar  tissue,  containing  a  few 
scattered  ganglion-cells. 

The  mucous  membrane  consists  of  a  highly  cellular  connective 
tissue  covered  with  ciliated  columnar  epithelium.  During  life  these 
cilia  propel  toward  the  uterine  cavity  substances  coming  into  con- 
tact with  them.  Toward  and  at  the  fimbriated  extremity  of  the 
tube  the  mucous  membrane  is  thrown  into  deep  longitudinal  folds, 
upon  which  are  numerous  secondary  and  tertiary  folds,  but  further 
toward  the  uterus  these  folds  give  place  to  branching  villous  pro- 
jections into  the  lumen  (Fig.  189).  Toward  the  uterine  end  of  the 
tube  these  complicated  folds  and  villi  disappear  and  the  lumen  of 
the  tube  becomes  round  or  stellate. 

3.  The  Uterus.  —  The  external  surface  of  the  uterus,  throughout. 
most  of  its  extent,  is  covered  by  a  reflection  of  the  peritoneum. 
Beneath  this  are  three  distinct  coats  of  smooth  muscular  tissue,  the 


212 


NORMAL  HISTOLOGY. 


outer  two  in  close  contact  with  each  other ;  the  two  inner  separated 
by  a  thin  layer  of  areolar  fibrous  tissue,  supporting  large  blood- 
vessels. This  separation  of  the  innermost  layer  from  the  middle 
layer  leads  to  the  inference  that  the  former  is  analogous  to  the  mus- 
cularis  mucosse  found  in  other  hollow  viscera,  although  in  the  uterus 
it  forms  the  chief  mass  of  the  muscular  tissue  of  the  organ.  The 
outer  layer  is  made  up  of  bundles  of  fibres  that  have  a  general 
longitudinal  position  ;  the  two  inner  layers  have  a  general  circular 


FIG.  189. 


Transverse  section  of  the  Fallopian  tube  near  its  free  end.  (Orthmann.)  Numerous  branch- 
ing villous  projections  of  the  wall,  covered  by  ciliated  columnar  epithelium,  extend  into 
the  lumen.  The  open  spaces  in  these  villous  projections  are  sections  of  the  bloodvessels. 

disposition  of  their  bundles,  though  the  latter  interlace  with  each 
other  in  various  directions  within  the  muscularis  mucosse,  leaving 
masses  of  areolar  tissue  containing  the  larger  bloodvessels  between 
them. 

Covering  the  surface  of  the  muscularis  mucosse  is  a  highly  cellu- 
lar connective  tissue,  not  unlike  granulation-tissue  in  appearance, 
except  that  it  is  less  richly  supplied  with  bloodvessels.  It  is  composed 
of  round  and  fusiform  cells,  lying  in  a  small  amount  of  intercellular 


Till-:  REPRODUCTIVE  ORGANS. 


213 


substance,  in  which  fibres  can  be  distinguished  only  with  difficulty. 
The  surface  of  the  mucous  membrane  is  covered  with  a  layer  of 
ciliated  columnar  epithelium,  which  is  continued  into  long  tub- 
ular glands  penetrating  the  superficial  portions  of  the  muscularis 
mucosae,  where  they  frequently  branch  before  terminating  in  blind 
extremities.  It  should  be  borne  in  mind  that  at  the  extremities  of 
these  glands  the  whole  tubule  is  often  filled  with  epithelial  cells,  so 
that  no  lumen  is  visible.  In  their  course  into  the  mucous  mem- 
brane these  glands  are  usually  straight  at  first,  but  in  their  deeper 
portions  become  tortuous  (Figs.  190  and  191). 

FIG.  190. 


Section  through  the  uterine  wall  of  a  rabbit ,  near  one  of  the  cornua.  (Schtiffer.)  m,  gland- 
ular portion  of  the  mucous  membrane ;  m,  m,  muscularis  mucosse ;  a,  submucosa  of  are- 
olar  tissue,  containing  the  large  bloodvessels  which  send  branches  into  the  stroma  of  the 
mucous  membrane;  cm,  circular  layer  of  the  muscular  coat;  lm,  longitudinal,  thicker 
layer  of  the  muscular  coat ;  s,  serous  coat,  derived  from  a  reflection  of  the  peritoneum. 

During  the  childbearing  period  of  life  the  portion  of  the  mucous 
membrane  resting  upon  the  muscularis  mucosse  is  the  seat  of  active 
changes  which  pass  through  a  cycle  corresponding  to  each  men- 
strual period,  but  interrupted  by  a  special  series  of  changes  during 


214 


NORMAL  HISTOLOGY. 


pregnancy.    These  changes  are  of  importance  in  their  bearing  upon 
the  pathology  of  the  organ,  and  must  be  briefly  described. 

At  the  menstrual  period  the  superficial  portion  of  the  mucous 
membrane,  down  to  its  muscular  coat,  suffers  a  degeneration,  which 
results  in  its  disintegration  and  discharge,  along  with  some  blood 
derived  from  the  exposed  and  damaged  vessels  of  small  size  within 
its  tissues.  After  this  degeneration  the  membrane  is  restored  by  a 
proliferation  of  the  elements  contained  between  the  bundles  of  the 
muscularis  mucosie,  the  glands  being  reformed  from  the  remnants 
of  their  deep  extremities.  The  mucous  membrane  slowly  continues 


Section  of  the  human  uterine  mucous  membrane  parallel  to  its  surface.  (Henle.)  1,  2,  3, 
uterine  glands  in  cross-section.  In  2,  the  basement-membrane  alone  is  represented,  the 
epithelium  having  fallen  out  of  the  section.  4,  bloodvessel  in  longitudinal  section.  Be- 
tween these  structures  is  the  highly  cellular  stroma  of  the  mucous  membrane,  only  the 
nuclei  of  its  cells  being  represented. 

to  increase  in  thickness  and  the  glands  in  tortuousness  until  the 
next  menstruation,  when  the  same  process  is  repeated.  It  will  be 
noticed  that  the  connective  tissue  of  the  mucous  membrane,  in  the 
absence  of  pregnancy,  is  subject  to  periodical  degeneration  and  re- 
generation, which  probably  prevent  its  development  into  a  mature 
fibrous  tissue  with  an  abundance  of  fibrillated  intercellular  substance. 
If  an  ovum,  discharged  from  the  ovary,  becomes  fertilized,  the 
menstrual  cycle  of  changes  in  the  superficial  portion  of  the  mucous 
membrane  of  the  uterus  is  interrupted.  That  portion  of  the  mu- 
cous membrane  then  undergoes  extensive  modifications  in  structure 
during  the  early  months  of  the  ensuing  pregnancy.  The  inter- 


THE  REPRODUCTIVE  ORGANS.  215 

cellular  tissue  between  the  uterine  glands  becomes  more  hyper- 
plastic  than  during  the  intervals  separating  the  menstrual  periods, 
and  at  the  same  time  the  cells  composing  it  become  hypertrophied, 
until  they  closely  resemble  large  epithelial  cells.  These  cells  have 
been  called  "decidual  cells."  The  ovum,  when  it  reaches  the 
cavity  of  the  uterus,  becomes  embedded  in  this  tissue,  which  grows 
around  and  encloses  it,  after  which  it  is  differentiated  into  three 
portions.  The  part  beneath  the  ovum  is  called  the  decidua  sero- 
tinti ;  that  which  invests  the  ovum,  the  decidua  reflexa ;  and  that 
lining  the  rest  of  the  uterine  cavity,  the  decidua  vera.  While  the 
decidual  tissue  is  developing  and  its  cells  enlarging  the  uterine 
glands  suffer  changes.  Their  mouths  become  widened,  and  their 
lower  portions  down  to  the  muscularis  mucosae  dilated,  after  which 
the  epithelial  lining  atrophies  and  seems  to  disappear,  so  that  the 
lamina  of  the  glands  appear  as  spaces  in  the  decidual  tissue.  As 
the  ovum  enlarges,  the  decidua  reflexa  comes  in  contact  with  the 
decidua  vera,  and  the  two  layers  exert  a  mutual  pressure  upon  each 
other,  which  flattens  the  spaces  they  contain  and  may  obliterate 
many  of  them.  The  decidual  tissue  now  consists  of  a  number  of 
flattened  spaces  which  are  separated  from  each  other  by  thin  walls 
of  fibrous  tissue  produced  by  the  further  development  of  the  de- 
cidual tissue.  The  decidua  reflexa  and  the  decidua  vera  blend 
with  each  other  to  form  a  part  of  the  membranes  that  are  expelled 
from  the  uterus,  along  with  the  placenta,  after  the  birth  of  the  child, 
the  rest  of  the  membranes  and  most  of  the  placenta  being  derived 
from  the  foetus.  After  the  birth  of  the  child  and  the  expulsion  of 
the  membranes  the  mucous  membrane  is  regenerated  from  the  tis- 
sues remaining  in  the  superficial  layers  of  the  muscularis  mucosse. 

The  mucous  membrane  of  the  cervical  portion  of  the  uterus  does 
not  participate  in  these  changes  incident  to  menstruation  and  preg- 
nancy, and  the  connective  tissue  underlying  its  epithelial  lining  is 
more  fibrous  in  character  than  that  in  the  corresponding  part  of  the 
uterine  body.  About  the  middle  of  the  cervical  canal  the  ciliated 
epithelium,  which  is  continuous  with  that  of  the  body,  passes  into 
a  stratified  epithelium,  which  extends  over  the  cervix  uteri,  the 
portio  vaginalis,  and  the  inner  surface  of  the  vagina  to  join  that  of 
the  epidermis  upon  the  labia  minora.  The  fibrous  tissue  beneath 
this  stratified  epithelium  possesses  papillae  similar  to  those  upon  the 
skin,  and  contains  mucigenous  glands,  which  secrete  a  tenacious 
mucus  serving  to  close  the  cervical  canal  during  pregnancy.  The 


216  NORMAL  HISTOLOGY. 

orifices  of  these  glands  sometimes  become  occluded,  causing  a  cys- 
tic dilatation  of  the  acini,  due  to  accumulated  secretion,  "  ovula 
Nabothi." 

The  muscular  and  other  tissues  of  the  uterine  wall  undergo 
hypertrophy  during  pregnancy,  the  individual  muscular  fibres  be- 
coming as  much  as  thirty  times  their  original  bulk  in  the  non-preg- 
nant uterus.  The  bloodvessels  also  enlarge  and  acquire  thicker 
walls.  These  retain  much  of  this  increase  of  size,  even  after  the 
involution  of  the  uterus  following  parturition,  but  the  muscular 
fibres  suffer  a  partial  fatty  degeneration,  which  restores  them  to 
nearly  their  original  condition. 

4.  The  Vagina  (Fig.  192). — The  subepithelial  fibrous  coat  of  the 
vagina  is  covered  with  small  papilla?,  which  project  into  the  epithe- 

FIG.  192. 


•ct 


• 


-"•«I--V 

Portion  of  a  longitudinal  section  of  the  vaginal  wall.  (Benda  and  Guenther's  Atlas.}  a, 
stratified  epithelium  ;  b,  subepithelial  areolar  tissue  ;  c,  muscularis  mucosse  ;  d,  areolar 
submucosa  containing  vascular  trunks  ;  e,  muscular  coat.  Outside  of  the  latter  is  the 
ill-defined  fibrous  coat,  not  represented  in  the  figure. 

Hum.  Outside  of  this  coat  is  one  of  smooth  muscular  tissue,  which 
is  not  clearly  divisible  into  layers,  but  in  which  the  inner  fibres  are 
chiefly  circular,  forming  an  imperfectly  defined  muscularis  mucosse, 
while  the  outer  have  a  longitudinal  direction,  and  may  be  regarded 
as  the  true  muscular  coat  of  the  vagina.  Outside  of  the  muscular 


THE  REPRODUCTIVE  ORGANS.  217 

coat  is  a  layer  of  areolar  tissue  connecting  the  vagina  with  the 
neighboring  parts,  except  at  its  posterior  and  upper  part,  where  it 
is  covered  with  a  serous  membrane,  forming  part  of  the  peritoneum. 

5.  The  External  Genitals. — The  hymen  is  a  fold  of  the  mucous 
membrane,  and  consists  of  fibrous  tissue  with  a  covering  of  strati- 
fied epithelium.  The  same  general  structure  obtains  also  in  the  labia 
minora,  prepuce,  and  labia  majora  ;  but  the  labia  minora  and  prepuce 
are  destitute  of  fat,  while  the  labia  majora  contain  considerable  adipose 
tissue.  All  three  organs  are  supplied  with  sebaceous  glands,  Avhich 
are  numerous  beneath  the  prepuce  and  are  associated  with  hairs  only 
on  the  labia  majora.  The  latter  also  contain  fibres  of  smooth  mus- 
cular tissue,  corresponding  to  the  analogous  dartos  of  the  scrotum. 
The  bulbi  vestibuli,  crura  of  the  clitoris,  and  the  body  and  glans  of 
that  organ  are  composed  of  erectile  tissue.  The  glands  of  Bartholin 
are  compound  racemose  glands,  in  which  the  alveoli  are  lined  with 
a  columnar  epithelium  resembling  in  structure  that  of  the  mucous 
glands  in  other  parts  of  the  body.  The  epithelium  lining  their 
ducts  is  of  the  cubical  variety. 

The  parovarium  is  a  remnant  of  the  Wolffian  body  of  the  foetus, 
consisting  of  a  series  of  blind  tubules  lined  with  epithelium  (Fig. 
185).  It  is  situated  between  the  Fallopian  tube  and  the  ovary.  The 
remains  of  the  Wolffian  duct  and  of  the  duct  of  Miiller,  having  a  sim- 
ilar structure  to  the  tubules  of  the  parovarium,  are  sometimes  per- 
sistent, the  one  connected  with  the  parovarium,  the  other  with  the 
extremity  of  the  Fallopian  tube.  These  structures  are  of  interest 
because  tumors  occasionally  arise  from  them. 

The  Maturation  of  the  Ovum. — Before  the  ovarian  ovum  is  ready 
for  fertilization  it  must  undergo  two  divisions,  during  which  the 
amount  of  chromatin  left  in  the  mature  egg  is  reduced  one-half. 
The  first  division  results  in  the  formation  of  two  cells,  which  differ 
enormously  in  the  amount  of  cytoplasm  they  possess,  but  which 
have  equal  shares  of  the  chromatin  in  the  original  nucleus.  The 
smaller  of  these  two  cells  is  known  as  the  "  first  polar  body."  After 
its  separation  from  the  larger  cell  both  cells  divide  again,  without 
an  intermediate  growth  of  the  chromatin.  In  this  second  division 
of  the  larger  cell  the  two  resulting  cells  are  again  very  unequal 
in  size,  the  smaller  being  the  "  second  polar  body."  The  first  polar 
body  having  also  divided,  there  result  from  these  successive  divis- 
ions one  mature  egg  and  three  polar  bodies,  each  with  only  half 
as  many  chromosomes  in  its  nucleus  as  are  commonly  found  in  the 


218  NORMAL  HISTOLOGY. 

general  or  "  somatic  "  cells  of  the  body  (Fig.  193).  The  polar  bodies 
perish,  as  does  also  the  ovum,  unless  fertilized  by  the  introduction 
of  a  spermatozoon.  The  latter,  as  we  shall  see,  also  contains  half 
the  number  of  chromosomes  contained  in  the  somatic  cells ;  so  that 

FIG.  193. 


Maturing  ovum  of  physa  (fresh-water  snail).  (Kostanecki  and  Wierzejski.)  Above  are  the 
two  small  cells  resulting  from  the  division  of  the  first  polar  body.  Below  is  the  ovum, 
the  nucleus  of  which  is  dividing  to  form  the  second  polar  body.  Near  the  centre  of  the 
ovum  is  the  nucleus  of  the  spermatozoon,  just  above  which  is  its  (divided)  centrosome 
with  surrounding  radiations  in  the  cytoplasm.  When  the  second  polar  body  has  been 
formed  the  chromosomes  remaining  in  the  ovum  will  be  ready  to  participate  with  those 
of  the  spermatozoon  in  the  further  development  of  the  then  fertilized  egg. 

after  its  entrance  into  the  mature  ovum  the  latter  acquires  its  full 
complement  of  chromosomes  and  is  ready  for  development. 

The  Mammary  Gland. — Each  mamma  consists  of  a  group  of  about 
twenty  similar  compound  racemose  glands,  opening  by  distinct  orifices 
at  the  tip  of  the  nipple,  and  separated  and  enclosed  by  fibrous  tissue, 
in  which  there  is  a  variable  amount  of  fat.  At  the  edges  of  the 
mamma  this  fibrous  stroma  becomes  continuous  with  the  tissues  of 
the  superficial  fascia  in  which  the  breast  is  situated. 

Each  of  the  glands  entering  into  the  composition  of  the  breast 
possesses  a  single  main  duct,  the  "  galactiferous  duct,"  which  is  lined 
with  columnar  epithelium,  except  near  its  orifice,  where  the  strati- 


THE  REPRODUCTIVE  ORGANS.  219 

fied  epithelium  of  the  epidermis  extends  for  a  short  distance  into 
its  lumen.  A  little  below  the  base  of  the  nipple  the  duct  presents 
a  fusiform  dilatation,  called  the  "  ampulla,"  which  serves  as  a  reser- 
voir for  the  comparatively  small  amount  of  milk  secreted  in  the 
intervals  between  nursings. 

The  main  duct  branches  in  its  course  from  the  nipple  into  the 
deeper  portions  of  the  gland,  and  these  branches  give  off'  twigs, 
which  terminate  in  the  alveoli  of  the  gland.  The  columnar  epithe- 
lium lining  the  main  duct  gradually  passes  into  a  cubical  variety 
in  the  branches,  and  this  becomes  continuous  with  the  epithelial 
lining  of  the  alveoli.  The  terminal  branches  of  the  ducts  are  short, 
so  that  the  alveoli  opening  into  them  lie  close  together  and  are  col- 
lectively known  as  a  "lobule"  of  the  gland.  These  lobules  are,  in 
turn,  grouped  into  lobes,  each  of  which  corresponds  to  one  of  the 
main  ducts  of  the  breast. 

The  individual  alveoli  and  the  lobules  are  surrounded  by  fibrous 
tissue,  which  may  be  subdivided  into  an  intralobular  and  an  inter- 
lobular  portion,  the  latter  more  abundant  than  the  former.  This 
fibrous  tissue  supports  the  vessels  and  nerves  supplied  to  the  gland. 

The  character  of  the  epithelium  lining  the  alveoli  varies  with  the 
functional  activity  of  the  gland. 

Before  puberty  the  secreting  acini  are  only  slightly,  if  at  all, 
developed,  the  mamma  consisting  of  a  little  fibrous  tissue  and  the 
ducts  of  the  gland,  which  possess  slightly  enlarged  extremities. 

When  the  gland  has  become  fully  developed,  at  or  about  puberty, 
the  epithelial  cells  lining  the  acini  are  small  and  granular  and  nearly 
fill  the  diminutive  lumina.  The  fibrous  stroma  is,  at  this  period, 
abundant  and  makes  up  the  chief  bulk  of  the  breast. 

When  the  gland  assumes  functional  activity  the  cells  enlarge 
and  multiply  (Fig.  194),  and  the  lumina  of  the  acini  become  dis- 
tinct and  filled  with  a  serous  fluid.  Into  this  fluid  a  few  fat-globules 
are  discharged  from  the  epithelial  lining,  forming  an  imperfect  milk, 
very  poor  in  cream  and  differing  in  the  proportions  of  the  dissolved 
constituents  from  the  milk  that  is  produced  after  the  function  of 
the  gland  is  fully  established.  This  secretion  is  called  "  colostrum." 
Besides  the  scant  supply  of  fat-globules  which  it  contains,  it  is  fur- 
ther characterized  by  the  presence  of  so-called  colostrum -corpuscles. 
These  are  leucocytes  which  have  wandered  into  the  acini  of  the 
gland  from  the  bloodvessels  in  the  interstitial  tissue,  and  have  taken 
some  of  the  fat-globules  of  the  secretion  into  their  cytoplasm.  This 


220  NORMAL  HISTOLOGY. 

process  results  in  an  enlargement  of  the  leucocyte,  and,  in  extreme 
cases,  to  an  obscuring  of  the  nucleus  and  cytoplasm  by  fat-globules, 
so  that  the  whole  appears  as  though  composed  of  an  agglutination 
of  numerous  drops  of  fat  (Fig.  195). 

As  the  functional  activity  of  the  gland  matures  the  epithelial 

FIG.  194.  FIG.  195. 


Fig.  191.— Dividing  epithelial  cells  from  the  mammary  gland  of  the  guinea-pig.  (Michaelis.) 
The  figure  represents  the  proliferation  of  the  cells  by  the  indirect  mode  before  lactation 
has  been  established — i.  e.,  during  the  maturation  of  the  gland. 

Fig.  195.  —  Colostrum-corpuscles  and  leucocytes  from  the  colostrum  of  a  guinea-pig. 
(Michaelis.) 

cells  lining  its  acini  produce  drops  of  fat  in  the  cytoplasm  bor- 
dering on  the  lumen,  and  these  are  subsequently  discharged  into 
the  lurnen,  forming  the  fat  or  cream  of  the  milk.  The  casein  of 
the  milk  appears  to  be  produced  in  the  following  manner :  it  has 
been  observed  that  during  lactation  the  nuclei  of  some  of  the  cells 
present  changes  in  form  that  lead  to  the  inference  that  they  undergo 
division  by  the  direct  mode — i.  e.9  without  passing  through  the 
phases  of  karyokinesis.  It  thus  happens  that  some  of  the  epi- 
thelial cells  contain  two  nuclei.  These  cells,  after  a  while,  project 
into  the  lumen  of  the  acinus,  the  two  nuclei  lying  in  a  line  perpen- 
dicular to  its  wall.  It  is  supposed  that  the  nuclei  nearest  the  lumen 
become  detached,  together  with  some  of  the  cytoplasm,  and  that  the 
chemical  constituents  of  the  nucleus  and  cytoplasm  enter  into  the 
formation  of  the  casein.  Such  free  nuclei  have  been  observed  in 
the  lumina  of  the  acini,  and  it  is  known  that  the  chromatin  which 
they  contain  disintegrates  and  eventually  disappears  (chromolysis), 
so  that  it  is  not  found  in  the  secreted  milk.  It  is  probable  that  the 
other  constituents  of  the  nucleus  likewise  undergo  chemical  changes 
(karyolysis)  (Fig.  196). 


THE  REPRODUCTIVE 


221 


When  lactation  is  suspended  the  breast  at  first  secretes  a  fluid  in 
every  way  resembling  colostrum,  and  eventually  returns  to  the  dor- 
mant state,  in  which  the  cells  are  again  small  and  granular  and  the 
stroma  is  relatively  abundant. 

As  the  glandular  portion  of  the  breast  enlarges  during  lactation, 
the  whole  breast  becomes  increased  in  size,  but  this  increase  is  not 
proportional  to  the  development  of  the  alveoli,  for  the  stroma  is 
reduced  in  amount,  so  that  the  lobules  of  the  gland  are  closer  to 
each  other.  After  the  period  of  lactation  is  passed  the  alveoli 
return  almost  to  their  original  size,  but  the  stroma  is  not  repro- 

FIG.  196. 


Section  from  the  mammary  gland  of  a  guinea-pig  during  lactation.  (Michaelis.)  The  figure 
represents  sections  of  two  acini  and  the  margin  of  a  third,  separated  by  vascularized 
areolar  tissue,  a,  fat-globule,  separated  from  the  lumen  by  a  mere  film  of  cytoplasm  ;  6, 
projecting  cell  with  two  nuclei :  c,  two  nuclei  which  appear  to  have  been  produced  by 
constriction  of  a  single  pre-existent  nucleus. 

duced  in  fibrous  form,  but  its  place  is  taken  by  adipose  tissue,  the 
amount  of  which  depends  upon  the  individual,  being  great  in 
those  that  are  fat,  and  slight  in  those  that  are  lean.  In  the 
latter,  therefore,  the  breast  becomes  soft  and  pendulous  after 
lactation  has  ceased. 

It  is  important  to  bear  the  above  changes  in  the  normal  gland  in 
mind  when  examining  the  mamma  for  evidences  of  a  tumor.  When, 
for  example,  the  stroma  is  abundant  and  the  glandular  structures 
undeveloped,  as  is  the  case  before  puberty,  sections  of  the  gland 
may  be  mistaken  for  those  of  a  mammary  fibroma. 


222  NORMAL  HISTOLOGY. 

The  nipple  is  composed  of  fibrous  tissue,  with  a  considerable 
admixture  of  elastic  fibres,  in  which  there  are  scattered  bundles  of 
smooth  muscular  tissue  lying  parallel  to  the  axis  of  the  nipple.  A 
circular  bundle  of  the  same  tissue  is  found  at  the  base  of  the  nipple, 
and  by  its  compression  on  the  bloodvessels  may  be  the  cause  of  the 
erection  of  the  nipple.  The  skin  at  the  base  of  the  nipple  and  in 
the  areola  surrounding  it  contains  large  sebaceous  glands. 

The  mammary  gland  in  the  male  is  functionless,  and,  while  it 
contains  the  same  structures  as  in  the  female,  it  remains  in  a  com- 
paratively undeveloped  condition. 

II.  IN  THE  MALE. 

The  male  organs  of  generation  include  the  penis,  prostate,  vesic- 
ulse  seminales,  vasa  deferentia,  epididyrnis,  and  testes,  together  with 
certain  accessory  glands. 

1.  The  Penis. — This  is  formed  by  three  parallel  structures :  the 
corpora  cavernosa,  lying  side  by  side  and  partially  blending  in  the 
median  line,  and  the  corpus  spongiosum,  situated  beneath  their  line 
of  junction  and  containing  the  urethra.  At  its  anterior  end  the 
corpus  spongiosum  expands  about  the  ends  of  the  corpora  cavernosa 
to  form  the  glans  penis.  These  three  bodies,  except  over  the  glans, 
are  firmly  held  together  by  fibrous  tissue,  which  is  condensed  at 
their  surfaces  to  form  compact  sheaths  or  external  coats  enveloping 
the  erectile  tissue  of  which  each  is  composed.  The  sheaths  of  the 
corpora  cavernosa  are  incomplete  where  they  are  in  contact,  permit- 
ting the  erectile  tissue  to  blend  in  the  median  line.  This  inter- 
communication is  freer  toward  the  anterior  end  of  the  penis  than 
near  its  root,  where  the  corpora  cavernosa  are  more  distinctly  sepa- 
rated, preparatory  to  their  divergence  to  form  the  crura. 

The  sheaths  of  the  corpora  cavernosa  are  composed  of  fibrous 
tissue  containing  an  abundance  of  elastic  fibres.  From  its  inner 
surface  each  sheath  gives  off  a  number  of  fibrous  bands,  called 
"  trabeculse,"  which  divide  and  anastomose  with  each  other,  forming 
the  chief  constituent  of  the  erectile  tissue.  Within  these  trabeculse 
are  numerous  bundles  of  smooth  muscular  tissue. 

The  erectile  tissue  is  made  up  of  these  trabeculse,  which  give  it  a 
spongy  character  and  are  covered  with  endothelial  cells,  converting  the 
spaces  between  them  into  cavernous  venous  channels.  These  become 
engorged  with  blood  during  erection.  The  vessels  supplying  this  blood 
are  situated  in  the  trabeculse,  and  give  off  capillary  branches,  which 


THE  REPRODUCTIVE  ORGANS. 


223 


FIG.  197. 


open  into  the  intertrabecular  spaces,  discharging  blood  into  those 
enormously  dilated  venous  radicles.  Here 
and  there  arterial  twigs,  surrounded  by  an 
investment  of  fibrous  tissue,  project  from  the 
trabeculae  into  the  venous  spaces.  These, 
because  of  their  twisted  forms,  have  received 
the  name  helicine  arteries  (Figs.  197  and  198). 
The  structure  of  the  corpus  spongiosum  is 

FIG.  198. 


Fig.  197.— Section  of  injected  corpus  cavernosum.    (Henle.)    a,  fibrous  capsule ;  6,  trabeculse ; 

c,  section  of  the  arteria  profunda  penis.    All  the  spaces  are  filled  with  the  material  used 

for  injection. 
Fig.  198. — Helicine  arteries.    A,  B,  C,  from  the  corpus  cavernosum;   D,  from  the  corpus 

spongiosum ;  *  *,  fibrous  bands  forming  a  part  of  the  trabecular  network. 

similiar  to  that  of  the  corpora  cavernosa,  but  the  trabeculse  are 
more  delicate  and  the  spaces  between  them  of  more  uniform  size. 
Its  sheath  is  studded  with  papillae  where  it  covers  the  glans,  at  the 
edge  of  which  they  are  unusually  large.  They  are  covered  with  a 
layer  of  stratified  epithelium,  which  conceals  them  over  the  surface 
of  the  glans,  where  they  are  comparatively  small,  but  merely  invests 
the  larger  ones  at  the  corona.  This  layer  of  epithelium  is  continu- 
ous with  that  of  the  skin  covering  the  rest  of  the  penis,  which  is 
elsewhere  loosely  connected  with  the  underlying  structures  by 


224 


NORMAL  HISTOLOGY. 


areolar  tissue  devoid  of  fat.  The  skin  is  without  hairs  on  the  ante- 
rior two-thirds  of  the  penis,  but  contains  sebaceous  glands,  which 
are  especially  numerous  in  the  fold  of  the  prepuce,  where  it  is 
attached  near  the  corona  of  the  glans,  glands  of  Tyson. 

2.  The  Prostate. — This  body  is  regarded  as  the  analogue  of  the 
uterus,  its  utricle  corresponding  to  the  cavity  of  that  organ.  It  has 
a  fibrous  investment,  which  merges  into  the  areolar  tissue  connect- 
ing the  prostate  with  the  surrounding  structures  and,  in  its  deeper 
portions,  contains  smooth  muscular  tissue,  which  accompanies  it  in 
forming  the  stroma  of  the  organ.  Within  this  stroma  are  the 
prostatic  glands,  composed  of  acini,  lined  with  epithelium  of  the 
columnar  variety,  and  opening  into  a  series  of  ducts  having  their 
orifices  in  the  floor  of  the  urethra.  The  glandular  alveoli  frequently 
contain  little  concretions  of  a  substance  closely  resembling  amyloid, 
corpora  amylacea,  which  often  display  a  marked  concentric  lamina- 
tion (Fig.  199). 

FIG.  199. 


Section  of  the  prostate.  (Heitzmann.)  Sections  of  one  acinus  and  portions  of  three  others 
are  included  in  the  figure.  These  are  surrounded  by  fibrous  tissue  traversed  by  bundles 
of  smooth  muscular  fibres.  E,  epithelial  lining  of  the  acini ;  M,  M,  smooth  muscular 
tissue ;  C,  concretions  of  amyloid  material,  showing  concentric  lamination. 


The  two  ejaculatory  ducts  pass  through  the  prostate  to  open  into 
the  urethra  in  its  course  within  that  organ.  A  little  behind  their 
orifices  is  the  verumontanum,  containing  erectile  tissue,  which  is 


THE  REPRODUCTIVE  ORGANS.  225 

supposed,  during  erection,  to  serve  as  a  dam,  preventing  the  entrance 
of  semen  into  the  bladder. 

The  ejaculatory  ducts  divide  behind  the  prostate,  one  branch 
forming  the  duct  of  the  seminal  vesicle,  while  the  other  becomes 
continuous  with  the  vas  deferens. 

3.  The  Seminal  Vesicles. — These  are  tubular  sacs  ending  in  blind 
extremities,  with  occasional  saccular  branches  given  oif  from  their 
sides.  They  are  lined  with  a  mucous  membrane  covered  with  columnar 
epithelium,  resting  upon  areolar  fibrous  tissue.     Outside  of  this  is 
a  muscular   coat  containing  internal  circular  and  external  longi- 
tudinal fibres,  and   surrounded  by  an  ill-defined  fibrous  coat  that 
passes  into  the  general  areolar  tissue  of  the  region.     The  seminal 
vesicles  sometimes  contain  semen,  for  which  they  may  serve  as  a 
temporary  reservoir,  but  they  also  secrete  a  fluid  that  is  mixed  with 
the  semen  at  the  time  of  ejaculation. 

4.  The  Vasa  Deferentia. — The  vas  deferens  of  each  side  resembles 
the  seminal  vesicle  in  structure.     It  is  lined  with  columnar  epi- 
thelium, beneath  which  is  a  layer  of  areolar  fibrous  tissue,  resting 
upon  the  muscular  coat.     This   is   surrounded  by  fibrous  tissue, 
becoming  areolar  as  it  blends  with  that  of  the  neighboring  parts. 
The  muscular  coat  is  thicker  than  that  of  the  seminal  vesicle,  and 
is  divisible  into  an  inner  layer  of  circular  and  an  outer  layer  of 
longitudinal  fibres.     The  mucous  membrane,  like  that  of  the  sem- 
inal vesicle,  is  thrown  into  folds,  which  are  longitudinal  throughout 
most  of  the  course  of  the  vas  deferens,  but  are  irregular  in  the 
sacculated  distal  portions  of  the  tube,  giving  the  surface  a  reticu- 
lated or  alveolar  appearance. 

5.  The  Epididymis. — The  vas  deferens  of  each  side  becomes  con- 
tinuous with  the  canal  of  the  epididymis,  which  is  an  enormously 
long  tube,  twenty  feet,  so  convoluted  and  packed  together  as  to 
occupy  but  little  space.     It  is  lined  throughout  with  columnar  epi- 
thelium, continuous  with  that  of  the  vas  deferens ;  but,  except  for  a 
short  distance  from  the  junction  with  the  vas,  the  cells  possess  cilia 
of  considerable  length,  which  induce  currents  toward  the  vas  deferensi 
The  muscular  coat  of  the  latter  is  continued  in  the  epididymis,  but 
is  very  thin.    Opening  into  the  canal  of  the  epididymis  are  the  vasa 
efferentia  of  the  testis. 

6.  The  Testis. — The  testis  is  a  compound  tubular  gland,  of  which 
the  secretion  contains  the  spermatozoa.     The  latter  are  derived  from 
certain  of  the  cells  lining  the  tubules,  and  contain  within  their 

15 


226  NORMAL  HISTOLOGY. 

structure  a  definite  amount  of  chromatin  and  a  centrosome.  During 
the  fertilization  of  the  ovum  this  chromatin  unites  with  a  similar 
amount  present  in  the  egg-cell,  and  thus  forms  a  complete  cell,  the 
nucleus  of  which  contains  equal  amounts  of  chromatin  from  the 
male  and  female  parents  of  the  future  offspring.  We  have  seen 
(Chapter  I.)  that  the  nuclei  of  the  cells  throughout  the  body  break 
up,  during  karyokinesis,  into  a  definite  and  constant  number  of 
fragments,  called  "  chromosomes,"  which  split  during  metakinesis ; 
one-half  of  each  chromosome  going  to  each  of  the  daughter-nuclei. 
These  chromosome-halves  form  a  reticulum  within  the  daughter- 
nuclei,  and  Avhile  in  that  form  the  chromatin  appears  to  increase  in 
amount,  so  that  by  the  time  the  cell  divides  again  the  full  supply 
of  chromatin  is  present  in  its  nucleus.  During  the  two  cell-divis- 
ions which  immediately  precede  and  result  in  the  formation  of  the 
spermatozoa  and  the  matured  egg  this  growth  of  the  chromatin 
does  not  take  place,  and,  as  we  shall  presently  see,  each  spermato- 
zoon or  matured  ovum  contains  but  half  of  the  chromosomes  that 
are  normally  present  in  the  somatic  or  general  cells  of  the  body.  This 
"  reduction  of  the  chromatin "  has  been  a  matter  of  much  study 
within  the  last  few  years,  because  of  its  probable  bearing  upon  the 
problems  of  heredity.  The  fact  of  its  occurrence  is  strongly  con- 
firmatory of  the  idea  that  the  chromatin  is  the  carrier  of  hereditary 
characteristics,  the  fertilized  ovum  receiving  equal  shares  from  both 
parents. 

The  tubular  glands  of  the  testis  are  enclosed  in  a  strong  fibrous  cap- 
sule, made  up  of  interlacing  bands  of  fibrous  tissue.  This  becomes  con- 
tinuous, behind,  with  a  mass  of  areolar  tissue  containing  the  vascular 
supply  of  the  organ  and  the  epididymis,  with  the  vasa  efferentia  open- 
ing into  it.  The  fibrous  capsule  is  called  the  "  tunica  albuginea."  It 
is  covered,  except  posteriorly,  by  the  visceral  portion  of  a  serous  mem- 
brane, the  "  tunica  vaginalis."  From  the  inner  surface  of  the  capsule 
numerous  bands  and  strands  of  fibrous  tissue,  trabeculse,  traverse  the 
glandular  part  of  the  organ,  imperfectly  dividing  it  into  lobes,  each 
of  which  contains  several  of  the  glandular  or  seminiferous  tubes. 

Upon  the  surfaces  of  the  trabeculse  and  upon  the  inner  surface 
of  the  capsule  the  dense  fibrous  tissue  of  those  structures  passes 
into  a  delicate  areolar  tissue,  which  gives  support  to  the  numerous 
small  bloodvessels  and  abundant  lymphatics  distributed  within  the 
organ.  This  vascular  areolar  tissue  also  penetrates  between  the 
seminiferous  tubules,  giving  them  support.  In  this  region  the 


THE  REPRODUCTIVE  ORGANS. 


227 


interstitial  tissue  just  mentioned  contains  large  cytoplasmic  cells 
of  connective-tissue  origin,  which  frequently  contain  globules  of 
fat  or  granules  of  pigment,  and  in  many  instances,  in  man,  have 
been  observed  to  contain  crystalloids  of  proteid  nature.  It  has 
been  surmised  that  these  cells  may  serve  for  the  storage  of  nutri- 
ment required  by  the  active  proliferation  of  the  cells  that  produce 
the  spermatozoa  within  the  seminiferous  tubes  (Fig.  200). 

FIG.  200. 


x&v-v 

'^•*  <^>;w.v 
-•^^•-^ 


• 


* 


, 


Interstitial  tissue  in  the  testis  of  the  cat.  (Plato.)  Three  bloodvessels  are  shown  in  either 
complete  or  partial  section.  Portions  of  two  seminiferous  tubules  are  represented  at  the 
upper  corners.  Between  these  structures  is  the  interstitial  tissue,  containing  large  cyto- 
plasmic cells.  This  tissue  is  rather  more  abundant  in  this  instance  than  in  the  human 
subject. 

Each  seminiferous  tube  is  provided  with  a  basement-membrane, 
upon  the  inner  surface  of  which  are  epithelial  cells.  These  are  di- 
visible into  three  groups  :  first,  a  parietal  layer  of  cells,  the  "  sper- 
matogonia,"  lying  next  to  the  basement-membrane ;  second,  a  layer 
of  cells,  often  two  or  three  deep,  called  the  "  spermatocytes,"  lying 
upon  and  derived  from  the  spermatogonia ;  third,  the  " spermatids," 
lying  most  centrally.  The  spermatids  are  derived  from  the  spermato- 
cytes, and  are  the  elements  from  which  the  spermatozoa  develop, 
one  spermatozoon  being  formed  from  each  spermatid. 

The  cells  of  the  parietal  layer,  that  containing  the  spermatogonia, 
are  not  all  alike.  At  intervals  certain  cells,  called  "  sustentacular  " 


228 


NORMAL  HISTOLOGY. 


cells,  or  the  "cells  of  Sertoli,"  are  differentiated  from  the  others  (Figs. 
201-213).     These  sustentacular  cells  rest  with  a  broad  base,  the 

FIG.  201. 


Superficial  aspect  of  the  parietal  cells  of  the  seminiferous  tube;  rat.  (Ebner.)  /,  basal 
plates  of  the  sustentacular  cells  (cells  of  Sertoli),  each  containing  a  large  vesicular 
nucleus,  poor  in  chromatin,  and  a  distinct  nucleolus  of  considerable  size ;  w,  spermato- 
gonia  resting  upon  the  basal  plates  of  the  cells  of  Sertoli.  Only  a  few  of  the  spermato- 
gonia  are  represented. 


FIG.  202. 


FIG.  203. 


hl'3 


w  1    /       M 


Sections  from  the  testis  of  the  rat,  illustrating  spermatogenesis.  (Ebner.) 
Figs.  202-213. — w,  spermatogonia  ;  /,  sustentacular  cells,  or  cells  of  Sertoli ;  h,  spermatocytes ; 
s,  spermatids  ;  sp,  spermatids  becoming  transformed  into  spermatozoa :  wl  to  wlO  traces 
the  history  of  the  spermatogonia  from  the  resting  condition  to  that  in  which  they  have 
grown  to  become  primary  spermatocytes.  During  this  process  they  move  from  the  parietal 
layer  into  that  covering  it.  fill,  a  recently  formed  spermatocyte ;  hl'2  to  tvlO,  growth  of 
the  spermatocyte;  ft21,  beginning  of  the  division  to  form  secondary  spermatocytes;  h'22, 
its  end;  A23,  secondary  spermatocyte,  with  chromatin  in  open  spirem;  h'24,  division  of 
the  secondary  spermatocyte  to  form  two  spermatids;  s25,  recently  formed  spermatid  ;  ,«26 
to  s29,  growtli  of  the  spermatid.  (By  this  time  the  preceding  crop  of  spermatozoa  is  fully 
developed  and  has  been  discharged  into  the  lumen  of  the  seminiferous  tube.)  s30  and 
«31,  beginning  transformation  of  the  spermatids  into  spermato/oa.  Their  cytoplasm 
blends  with  that  of  the  sustentacular  cell.  sp32  to  sp39,  stages  in  the  differentiation  of 
the  spermatozoa;  40,  completed  spermatozoon  ready  to  pass  into  the  lumen  of  the  tube. 
wl  (Fig.  212)  and  wll  (Fig.  213)  illustrate  the  division  of  the  spermatogonia  before  they 
begin  to  develop  into  spermatocytes.  It  is  supposed  that  the  sustentacular  cells  aid  in 
the  nourishment  of  the  spermatids  during  their  transformation  into  spermatozoa,  and 
that  after  the  discharge  of  the  latter  the  cytoplasmic  process  is  retracted  toward  the  base- 
ment-membrane, bringing  with  it  the  globules  of  fat  and  cytoplasmic  fragments  of  the 
spermatids  represented  by  dark  spots  and  small  round  bodies  in  nearly  all  the  figures. 
This  retraction  is  taking  place  at/,  Fig.  204.  The  cells  of  Sertoli  do  not  appear  to  mul- 
tiply ;  at  least  no  karyokinetic  figures  have  been  observed  in  their  nuclei. 


THE  REPRODUCTIVE  ORGANS. 


229 


FIG.  204. 


FIG.  205. 


s'3l 


*.#&1        A, 
Jj    If 

B|» 

f 

sfl  ^kui6 


-inx  ?  A.^iyfov'  x-^  O/v\ 


w  4      /      « 


FIG.  207. 


A  18 


FIG.  209. 


h  20 


/         tr  8     w 


230  NORMAL  HISTOLOGY. 

FIG.  210.  FlG-  211- 


h22 


£^W: 

4$k  IT 


•    '/(<  •  '  1   '          l*W^^B^n 

j),  ;[v      •;  -^3e   _  ^;i!/Mi1j 

^l^ll»W)liM^ 


p 


^KW^)  / 

h  24      /£ 


mftL- 

r^/«rx-''%- ' 


w  w9 


FIG.  212. 


s26< 


l 


w    folO   /  ^ 

FIG.  213. 


w  J/     / 


THE  REPRODUCTIVE  ORGANS. 


231 


FIG.  214. 


— d 


"basal  plate,"  directly  upon  the  basement-membrane,  where  the 
edges  of  the  basal  plates  are  in  contact,  forming  a  sort  of  bed 
with  depressions  in  its  upper  surface,  in  which  the  spermatogonia 
find  lodgement.  The  cells  of  Sertoli  possess  a  thick  cytoplasmic 
process,  which  extends  toward  the  lumen  of  the  tubule,  and  to 
which  those  spermatids  which  are  developing  into  spermatozoa 
become  attached.  For  this  reason  they  are  called  sustentacular 
cells.  Their  nuclei  diifer  from  those  of  the  neighboring  spermato- 
gonia in  being  less  rich  in  chromatin  and 
in  possessing  a  single  and  prominent  nu- 
cleolus. 

The  appearances  of  the  various  cells 
enumerated  depend  upon  the  stage  in 
their  activity  which  happens  to  be  under 
observation.  The  general  course  of  de- 
velopment, ending  in  the  formation  of 
the  spermatozoa,  is  as  follows :  the 
spermatogonia,  between  the  cells  of  Ser- 
toli, multiply  until  quite  a  collection  of 
such  cells  is  produced.  Each  division  is 
followed  by  a  period  of  rest,  during  which 
the  chromatin  increases  in  amount.  When 
the  final  stage  of  rest  is  at  an  end  and  the 
cells  have  attained  their  maturity,  they 
constitute  what  are  called  the  primary 
spermatocytes.  These  now  divide,  each 
forming  two  secondary  spermatocytes, 

which    in    turn    divide,     without    an    inter-    Human spermatozoa.  (Bohm and 

mediate  distinct  res  ting-stage,  to  form 
two  spermatids.  Each  primary  spermato- 
cyte,  therefore,  gives  rise  to  four  sperm- 
atids. It  is  during  the  division  of  the 
secondary  spermatocytes  that  the  reduc- 
tion in  chromatin,  which  was  mentioned 
above,  takes  place  (Figs.  202-213).  Each 
spermatid  receives,  in  addition  to  its  por- 
tion of  chromatin,  a  single  centrosome. 

The  spermatozoon,  then,  is  derived  from  a  corpuscle,  the  spermatid, 
which  contains  all  the  essential  organs  of  a  cell,  differing  from  the  gen- 
eral cells  of  the  body,  the  somatic  cells,  only  in  possessing  half  the 


e 


Davidoff,  after  Retzius  and 
Jensen.)  The  left  figure  repre- 
sents the  side  view  and  the 
middle  figure  surface-view  of 
a  spermatozoon,  a,  head  (nu- 
cleus) ;  6,  end-knob  (centro- 
some?): c,  middle  piece;  d, 
tail  of  flagella;  e,  end-piece. 
The  thickness  of  d  may  be 
owing  to  the  presence  of  a 
sheath  surrounding  the  actual 
flagella,  which  projects  from 
the  sheath  at  e. 


232  NORMAL  HISTOLOGY. 

usual  number  of  chromosomes  in  its  nucleus.  It  is  unnecessary  to 
pursue  the  chain  of  events  through  which  the  spermatid  gives  rise  to 
the  spermatozoon.  It  may  suffice  to  state  that  the  body  of  the  latter 
consists  of  the  chromatin  of  the  nucleus ;  that  the  long  cilium  con- 
stituting the  tail  of  the  spermatozoon  is  developed  from  the  cyto- 
plasm ;  and  that  the  centrosome  of  the  spermatid  is  probably  con- 
tained in  the  middle  piece  of  the  spermatozoon  (Fig.  214).  Even 
these  conclusions  are  inferences  from  studies  of  spermatogenesis 
in  the  lower  animals,  and  not  from  direct  studies  of  that  process  in 
man.  The  latter  undoubtedly  conforms  very  closely  to  the  former 
in  all  essential  details. 

To  return  to  the  histology  of  the  test-is  :  the  epithelial  cells  of  the 
seminiferous  tubules  rest  upon  a  basement-membrane,  which  is  divis- 

FIG.  215. 


in- 


Basement-membrane  from  seminiferous  tube  of  the  rat.  (Ebner.)  in,  endothelial  cells  com- 
posing the  external  layer  ;  I,  cells,  presumably  leucocytes,  intercalated  between  the  endo- 
thelial cells.  The  faint  striations  upon  the  endothelial  cells  represent  wrinkles  in  the 
homogeneous  membrane  forming  the  inner  surface  of  the  basement-membrane ;  the 
wrinkling  is  probably  due  to  a  slight  shrinkage  of  the  endothelium. 

ible  into  two  layers :  first,  an  internal,  extremely  delicate,  homoge- 
neous membrane,  upon  which  the  epithelial  cells  rest ;  and,  second, 
a  layer  of  endothelial  cells  (Fig.  215).  The  latter  may  bound,  at 
least  in  places,  the  lymphatic  spaces,  which  are  abundant  in  the 
interstitial  tissue  of  the  testis. 

Toward  the  back  of  the  testis  the    seminiferous  tubules  unite 


THE  REPRODUCTIVE  ORGANS.  233 

with  each  other  and  open  into  a  number  of  straight  ducts  of 
smaller  diameter,  called  the  "  vasa  recta."  These  are  lined  with 
a  cubical  epithelium  resting  upon  an  extension  of  the  basement- 
membrane  of  the  seminiferous  tubes,  and,  in  turn,  open  into  a 
reticulum  of  tubules  of  larger  diameter,  situated  in  the  mass  of 
areolar  tissue  at  the  posterior  aspect  of  the  testis.  This  reticulum 
is  called  the  "  rete  vasculosum,"  and  the  tubules  composing  it  are 
lined  with  a  low  epithelium,  apparently  resting  upon  the  surround- 
ing fibrous  tissue,  without  an  intermediate  basement-membrane. 
These  tubes  permit  an  accumulation  of  semen  before  it  enters  the 
vasa  efferentia. 

The  vasa  efferentia  have  a  peculiar  epithelial  lining,  which  may 
be  regarded  as  transitional  between  the  cubical  epithelium  of  the 
vasa  recta  and  rete  and  the  ciliated  columnar  variety  lining  the 
epididymis.  It  consists  of  alternating  groups  of  cubical  and 
ciliated  columnar  epithelial  cells  (Fig.  216). 

FIG.  216. 


Section  of  vasa  efferentia  from  human  testis.  (Bohm  and  Davidoff.)  a,  cubical  or  secretory 
epithelium ;  b,  columnar  ciliated  epithelium,  with  deeper  pyramidal  cells  beneath  those 
that  bear  the  cilia.  This  form  of  ciliated  epithelium  corresponds  to  that  found  in  the 
epididymis  where  the  cubical  epithelium  is  absent. 

The  vasa  efferentia,  as  already  stated,  open  into  the  canal  of  the 
epididymis,  through  which  their  contents  reach  the  vas  deferens. 
The  walls  of  the  efferent  tubes  possess  a  layer  of  encircling  smooth 
muscular  fibres,  which  are  reinforced  in  the  epididymis  by  an  addi- 
tional external  layer  of  longitudinal  fibres. 

The  nerves  supplied  to  the  testis  are  destitute  of  ganglia,  and  are 
distributed  to  the  vessels  and  surfaces  of  the  seminiferous  tubules. 
No  terminations  have  been  traced  to  the  epithelial  lining  of  those 
tubules. 


CHAPTER   XVIII. 

THE  CENTRAL  NERVOUS  SYSTEM. 

THE  functional  part,  or  parenchyma,  of  the  central  nervous 
system  is  composed  of  ganglion- cells  with  their  processes.  Some 
of  these  processes  are  of  cytoplasmic  nature,  and,  as  explained  in 
the  chapter  on  the  elementary  tissues,  are  called  the  protoplasmic 
processes.  From  each  ganglion-cell  at  least  one  process  is  given 
oif  which  differs  from  the  protoplasmic  processes,  and  is  called  the 
"axis-cylinder  process."  This  in  most  cases  becomes  the  axis- 
cylinder  of  a  nerve-fibre,  and  may  be  invested  with  a  medullary 
sheath  and  neurilemma  at  some  point  near  or  at  some  distance  from 
its  exit  from  the  cell. 

It  will  be  convenient,  for  the  brief  description  of  the  central 
nervous  system  to  which  this  chapter  must  be  restricted,  to  adopt  a 
special  terminology  for  the  different  portions  of  the  ganglion-cell 
and  its  processes,  as  follows  :  the  term  ganglion-cell  will  be  restricted 
to  the  nucleus  and  the  cytoplasm  surrounding  it ;  the  protoplasmic 
processes  will  be  called  the  dendrites,  and  their  terminations 
the  teledendrites.  The  axis-cylinder  process  will  be  termed  the 
neurite;  the  delicate  branches  it  may  give  off  in  its  course,  the 
collaterals;  and  the  terminal  filaments  of  the  main  trunk,  col- 
lectively the  teleneurites.  The  cell,  with  its  processes  and  their 
terminations,  will  collectively  constitute  a  neuron. 

A  complete  neuron,  then,  consists  of  (1)  certain  teledendrites,  which 
unite  to  form  one  or  more  dendrites  connecting  them  with  the  gan- 
glion-cell ;  (2)  the  cell  itself;  and  (3)  one  or  more  neurites,  which  may 
give  off  collaterals  and  finally  terminate  in  teleneurites  (Fig.  217). 

At  the  present  time  these  neurons  are  believed  to  be  without 
actual  connection  with  each  other,  but  to  convey  nervous  stimuli  by 
contact.  The  course  of  the  nervous  impulses  is  from  the  teleden- 
drites to  the  nerve-cell,  and  thence,  by  way  of  the  neurite,  to  the 
teleneurites,  whence  it  is  communicated,  without  a  direct  structural 
union,  to  the  next  tissue-element  in  the  chain  of  nervous  transmis- 
sion. Those  neurites  which  carry  stimuli  from  the  nerve-centres 

234 


THE  CENTRAL  NERVOUS  SYSTEM. 


235 


to  the  periphery,  centrifugal  impulses,  form  the  axis-cylinders  of 
some  of  the  nerves.  The  axis-cylinders  of  those  nerves  which 
convey  impulses  from  the  periphery  toward  the  nervous  centres, 

FIG.  217. 


II 


Sketch  illustrating  the  composition  of  neurons.  I,  a  neuron  transmitting  centrifugal 
impulses.  II,  a  neuron  receiving  and  transmitting  centripetal  impulses.  Ill,  a  neuron, 
the  function  of  which  is  supposed  to  be  the  distribution  of  impulses  within  the  nerve- 
centre  in  which  it  is  situated,  a,  ganglion-cell ;  6,  dendrite ;  c,  teledendrites ;  d,  neurite ; 
e,  collaterals ;  /,  teleneurites.  In  II  the  body  c  represents  some  sensory  organ  imparting 
nervous  impulses  to  the  teledendrites  of  a  sensory  nerve.  The  nervous  filament  g  is  a 
neurite,  presumably  derived  from  the  sympathetic  nervous  system,  leading  to  teleneu- 
rites applied  to  a  ganglion-cell,  a,  of  a  posterior  spinal  ganglion.  The  portion  h  of  the 
"nerve"  springing  from  that  cell  is  regarded  as  a  portion  of  the  cell  itself.  In  the 
embryonic  condition  the  dendrite  and  neurite  both  spring  directly  and  separately  from 
the  body  of  the  cell,  the  portion  h  being  a  subsequent  development,  i,  endothelial 
envelope  surrounding  the  ganglion-cell.  Ill  represents  a  ganglion-cell,  apparently  devoid 
of  distinct  dendrites,  but  having  numerous  processes  that  at  first  appear  protoplasmic, 
but  soon  assume  the  characters  of  neurites.  These  cells  are  found  in  the  retina  and 
olfactory  bulb,  and  have  been  termed  spongioblasts,  cellulas  amacrinas,  and  parareticu- 
lar  cells.  It  is  thought  that  nervous  stimuli  are  received  directly  by  the  cytoplasm  of 
the  cell,  without  the  intermediation  of  dendrites.  x  represents  the  omission  of  a  portion 
of  a  fibre.  The  arrows  indicate  the  directions  taken  by  nervous  impulses. 


centripetal  stimuli,  may  be  the  dendrites  connected  with  ganglion- 
cells  in  or  near  those  centres ;  c.  </.,  in  the  posterior  root-ganglia  of 
the  spinal  nerves,  or  they  may  be  the  neurites  springing  from 


236 


NORMAL  HISTOLOGY. 


peripheral  ganglion-cells,  as  is  exemplified  in  many,  if  not  all,  of 
the  organs  of  special  sense. 

I.   THE   SPINAL   CORD. 

The  axis  of  the  spinal  cord  is  composed  of  a  column  of  gray 
matter  containing  numerous  ganglion-cells  and  nervous  filaments 
held  in  position  by  a  cement- substance,  neuroglia-cells,  the  fibrous 
prolongation  of  the  ependyma  cells  lining  the  central  canal,  and  a  little 
fibrous  tissue  accompanying  the  vessels  derived  from  the  pia  mater. 

Fio.  218. 


FIGS.  218  and  219.— Transverse  sections  of  human  spinal  cord.    (Schafer.) 
Fig.  218,  from  the  lower  cervical  region ;  Fig.  219,  from  the  middle  dorsal  region,  a,  b,  c,  groups 
of  ganglion-cells  in  the  anterior  horn ;  d,  cells  of  the  lateral  horn ;  e,  middle  group  of 
cells ;  /,  cells  of  Clarke's  column ;  g,  cells  of  posterior  horn ;  c,  c,  central  canal ;  a,  c,  an- 
terior commissure  of  white  matter. 


THE  CENTRAL  NERVOUS  SYSTEM. 


237 


POSTERIOR 
ROOT 

BUNDLES 


JANTERO- 
| LATERAL 

\ASCENDINO- 

X 


Transverse  section  of  human  spinal  cord,  from  the  middle  lumbar  region.  (Schafer.)  a  6,  c, 
groups  of  ganglion-cells  in  the  anterior  horn ;  d,  cells  of  the  lateral  horn ;  e,  middle 
group  of  cells ;  /,  cells  of  Clarke's  column ;  g,  cells  of  posterior  horn ;  c.  c,  central  canal ; 
a,  c,  anterior  commissure  of  white  matter. 

In  cross-section  this  column  of  gray  matter  presents  a  transverse 
central  portion,  the  gray  commissure,  near  the  middle  of  which  is 
the  central  canal.  At  each  side  this  gray  commissure  blends  with 
masses  of  gray  matter,  occupying  nearly  the  centre  of  each  lateral 
half  of  the  cord  and  having  a  general  crescentic  form.  The  ends 
of  these  crescentic  masses  form  the  anterior  and  posterior  cornua 
of  the  gray  matter,  from  which  the  anterior  and  posterior  roots  of 
the  spinal  nerves  proceed.  The  anterior  cornua  are  larger  than  the 
posterior  and  contain  larger  ganglion-cells. 

Surrounding  the  column  of  gray  matter  everywhere,  except  at 
the  bottom  of  the  posterior  median  fissure  of  the  cord,  and  the 
interruptions  formed  by  the  nerve-roots  in  their  exit  from  the  gray 
matter,  is  a  layer  of  white  matter,  formed  of  medullated  nerve- 
fibres  running  parallel  with  the  axis  of  the  cord  and  held  together 
by  neuroglia  and  delicate  vascularized  fibrous  bands  proceeding 
from  the  deep  surface  of  the  pia  mater. 

The  white  matter  of  the  cord  has  been  divided  into  a  number  of 
columns,  for  the  most  part  indistinguishable  through  structural  dif- 
ferences, but  each  containing  fibres  that  play  similar  functional  roles. 
These  columns,  with  their  names,  are  indicated  in  Figs.  218,  219, 
and  220.  The  columns  of  Goll  and  Burdach,  forming  the  posterior 


238 


NORMAL  HISTOLOGY. 


column  of  the  white  matter,  between  the  posterior  cornua  and  the 
posterior  median  fissure,  conduct,  for  the  most  part,  centripetal 
impulses.  Impulses  having  the  same  upward  direction  are  also 
conveyed  by  the  direct  cerebellar  tract  and  the  tract  of  Gowers  in 
the  lateral  column  of  the  white  matter.  Centrifugal  impulses, 
motor  stimuli,  are  conveyed  by  the  fibres  in  the  direct  pyramidal 
tract  of  the  anterior  column  and  by  those  of  the  crossed  pyramidal 

FIG.  221. 


Diagram  of  spinal  cord,  illustrating  the  associations  of  its  various  nervous  elements.  (R.  y 
Cajal.)  a,  collateral  from  Goll's  tract,  entering  into  the  formation  of  the  posterior  com- 
missure ;  b,  collateral  to  the  posterior  horn ;  c,  collateral  to  the  formatio  reticularis  and 
the  anterior  horn ;  d,  posterior  nerve  neurite,  with  its  collaterals  ;  e,  collaterals  from  the 
lateral  column ;  /,  collaterals  to  the  anterior  commissure  ;  g,  central  canal ;  h,  neurite  in 
the  crossed  pyramidal  tract  from  the  commissure-cell  of  the  opposite  side  ;  i,  its  course 
in  the  commissure ;  j,  neurite  from  a  large  motor  cell  in  the  anterior  horn  k ;  I,  cell  of 
the  anterior  horn,  giving  off  a  neurite  dividing  into  an  ascending  and  a  descending 
branch  (compare  Fig.  224,  D) ;  m,  commissure-cell ;  n,  cell  giving  off  a  collateral  within 
the  gray  matter ;  o,  neurite  of  the  cell  u,  in  Clarke's  column  ;  p,  neurite  from  the  mar- 
ginal cell  s,  of  the  substance  of  Rolando ;  q,  cross-section  of  an  axis-cylinder  (neurite) 
in  the  white  substance  of  the  cord  ;  r,  division  of  a  posterior  nerve-fibre  (neurite)  into 
ascending  and  descending  branches ;  t,  small  cell  in  the  substance  of  Rolando.  Aside 
from  the  cells  indicated  in  the  figure,  the  gray  matter  contains  some  that  give  off  neurites 
which  divide  into  two  or  three  branches  while  in  the  gray  matter,  the  branches  going 
to  different  columns  of  white  matter.  There  are  also  cells  with  very  short  neurites, 
which  terminate  in  teleneurites  within  the  gray  matter,  and  probably  distribute  nervous 
impulses  for  short  longitudinal  distances. 


tract  in  the  lateral  column.  The  tracts  hitherto  considered  contain 
fibres  that  are  continued  into  the  higher  nerve-centres  of  the  brain 
and  cerebellum,  to  or  from  which  they  convey  nervous  impulses. 
But  the  spinal  cord  is  not  merely  a  collection  of  such  transmitting 


THE  CENTRAL  NERVOUS  SYSTEM.  239 

fibres.  It  is  also  a  nerve-centre  of  complex  constitution,  in  which 
neurons  terminate  in  teleneurites  or  arise  in  teledeudrites. 

Some  of  the  neurons  within  the  cord  are  confined  to  its  substance, 
and  constitute  nervous  connections  between  the  different  parts  at 
various  levels.  These  may  be  termed  longitudinal  cornmissural 
neurons,  or  association-fibres.  Portions  of  such  neurons  are  repre- 
sented in  the  diagram  of  a  cross-section  of  the  cord  (Fig.  221), 
which  also  contains  representations  of  some  of  the  neurites  in  the 
posterior  spinal  nerve-roots,  with  their  collaterals  ending  in  tele- 
neurites within  the  gray  matter  (d).  On  the  right  side  of  the  figure, 
the  nerve-cells,  Avith  their  dendrites  and  the  beginning  of  the  neu- 
rites, are  shown.  On  the  left  side  the  neurites  connected  with  cells 
at  another  level  are  shown,  re-entering  the  gray  matter,  where  they 
terminate  in  teleneurites.  In  studying  this  figure  it  must  be  borne 
in  mind  that  the  teledendrites  of  the  neurons  on  the  right  are  in 
close  relations  with  the  teleneurites  of  other  neurons,  and  that  the 
teleneurites  represented  on  the  left  are  in  close  relations  with  the 
teledendrites  of  other  neurons.  These  association-neurons  are, 
therefore,  merely  links  in  chains  of  communicating  neurons.  They 
are  again  represented  in  Fig.  224,  D  and  E. 

Aside  from  these  association-neurites,  the  gray  matter  of  the 
cord  receives  innumerable  collaterals  from  the  neurites  forming  the 
axis-cylinders  of  the  nerves  in  the  various  columns  of  the  white 
matter.  These  collaterals  terminate  in  teleneurites,  which  are  in 
close  relations  with  the  teledendrites  of  the  neurons  arising  in  the 
cord.  The  distribution  of  these  collaterals  is  represented  in  Fig. 
222.  The  collaterals  from  the  anterior  column  enter  the  anterior 
horn  of  the  gray  matter,  where  they  are  chiefly  distributed  about 
the  large  ganglion-cells  in  the  antero-lateral  portion  of  its  substance 
(Fig.  218,  6;  Fig.  221,  j),  but  may  also  extend  to  other  parts  of 
the  gray  matter.  The  collaterals  from  the  fibres  in  the  lateral 
columns  of  the  white  matter  are  most  numerous  near  the  pos- 
terior horn,  which  they  enter,  many  of  them  passing  through  the 
gray  matter  behind  the  central  canal  and  forming  a  part  of  the 
posterior  or  gray  commissure  of  the  cord  (Fig.  222,  I).  The  col- 
laterals from  the  posterior  column  are  divisible  into  four  groups : 
first,  those  which  are  given  off  in  the  lateral  portion  of  that  column 
(Fig.  222,  G),  and  are  distributed  in  the  outer  portion  of  the  pos- 
terior horn  and  in  the  substance  of  Rolando  (Fig.  222,  I) ;  second, 
those  which  end  in  Clarke's  column  (Fig.  222,  J) ;  third,  those 


240 


NORMAL  HISTOLOGY. 


which  arise  chiefly  in  the  column  of  Goll,  pass  through  the  sub- 
stance of  Rolando,  and  then  form  an  expanding  bundle  distributed 
in  the  anterior  horn  of  the  gray  matter,  where  they  are  in  associa- 
tion with  the  dendrites  of  the  motor  cells  in  that  region  (these 
fibres  form  the  reflex  bundle  of  Kolliker,  Fig.  222,  H) ;  fourth, 
collaterals  springing  from  fibres  in  the  posterior  column,  passing 


Cross-section  of  the  spinal  cord  of  a  newborn  child,  showingthe  distribution  within  the  gray 
matter  of  the  collaterals  from  the  neurites  of  the  white  matter.  (R.  y  Cajal.)  a,  anterior 
fissure ;  B,  pericellular  branches  of  the  collaterals  from  the  anterior  column  ;  C,  collaterals 
of  the  anterior  commissure;  D,  posterior  bundle  of  collaterals  in  the  posterior  commis- 
sure ;  E,  middle  bundle  of  the  posterior  commissure ;  /,  anterior  bundle  ;  G,  collaterals 
from  the  posterior  column ;  H,  senso-motory  collaterals  from  the  posterior  column ; 
I,  pericellular  terminations  of  collaterals  in  the  posterior  horn  ;  J,  collateral  terminations 
in  the  column  of  Clarke. 

through  the  posterior  commissure  of  gray  matter  and  ending  in  the 
substance  of  Rolando  of  the  opposite  side  (Fig.  222,  D). 

The  reflex  collaterals  arising  in  the  posterior  column  are  shown 
in  Fig.  223,  where  their  teleneurites  are  in  close  relations  with  the 
teledendrites  of  the  motor  cells  e. 

The  centripetal  or  sensory  neurites  of  the  posterior  spinal  nerve- 
roots  spring  from  the  ganglion-cells  of  the  spinal  ganglia.  When 
they  have  entered  the  white  matter  of  the  spinal  cord  they  divide 


THE  CENTRAL  NERVOUS  SYSTEM. 


241 


into  two  branches  (Fig.  221,  /•).  One  of  these  ascends  in  the  white 
substance  and  the  other  descends.  Both  branches  give  off  numer- 
ous collaterals,  which  penetrate  the  gray  matter,  ending  in  teleneu- 
rites  associated  with  the  teledendrites  of  the  cells  in  both  the  ante- 
rior and  the  posterior  horns,  and  the  column  of  Clarke.  The  main 
branches  of  the  sensory  neurite  also  enter  the  gray  matter,  after 


FIG.  223. 


FIG.  224. 


Fig.  223.— Diagram  of  the  senso-motory  reflex  collaterals  in  the  cord.  (R.  y  Cajal.)  a,  gan- 
glion-cell of  the  posterior  nerve-root ;  b,  division  of  its  neurite  into  ascending  and  de- 
scending branches ;  c,  collaterals  to  anterior  horn ;  d,  terminal  teleneurites  in  the  pos- 
terior horn ;  e,  motor  cell  of  the  anterior  horn,  with  its  processes. 

Fig.  2'24.— Longitudinal  section  of  a  part  of  the  spinal  cord,  including  a  posterior  nerve-root. 
Semidiagrammatic.  (R.  y  Cajal.)  A,  posterior  nerve-root;  S,  white  substance  of  the 
cord  ;  O,  gray  matter ;  B,  collateral  teleneurites  in  the  gray  matter ;  C,  cell  with  a  single 
ascending  neurite  ;  D,  cell  with  bifurcating  neurite,  terminating  at  Fand  I;  E,  cell  with 
a  single  descending  neurite ;  F,  G,  terminal  teleneurites ;  a',  collateral  from  a  branch 
of  the  posterior  root-neurite  ;  6',  collateral  from  the  main  neurite  before  its  bifurcation. 

following  the  posterior  column  for  a  short  distance,  and  end  in  tele- 
neurites among  the  cells  of  the  posterior  horn  and  the  substance  of 
Rolando.  The  collaterals  which  pass  to  the  anterior  horns  (Fig. 
222,  H,  and  Fig.  223,  c)  have  to  do  with  the  origin  of  reflex  cen- 

ifi 


242 


NORMAL  HISTOLOGY. 


trifugal  impulses  emanating  from  the  motor  cells  in  that  region 
(Fig.  223,  e,  and  Fig.  221,  j).  The  further  transmission  of  these 
centripetal  stimuli  toward  the  higher  nerve-centres  of  the  brain 
probably  takes  place :  first,  through  the  cells  in  the  posterior  horns, 
the  neurites  from  which  pass  into  the  lateral  columns  and  there 
ascend  the  cord ;  second,  through  the  cells  of  Clarke's  column, 
which  also  send  neurites  into  the  lateral  column,  where  they  enter 
the  direct  cerebellar  tract  (Fig.  221,  o  •  see  also  Fig.  224).  In 
addition  to  these  centripetal  or  sensory  neurites,  the  posterior  nerve- 
roots  contain  a  few  centrifugal  neurites. 

FIG.  225. 


Diagram  of  a  sensory  and  a  motor  tract.  (R.  y  Cajal.)  A,  psycho-motor  region  in  cerebral 
cortex ;  B,  spinal  cord ;  C,  voluntary  muscle ;  D,  spinal  ganglion ;  D',  skin  ;  a,  axis-cylin- 
der of  a  neuron  extending  from  the  cerebral  cortex  to  the  anterior  horn  of  the  spinal 
cord,  where  the  terminal  teleneurites  are  in  relations  with  the  teledendrites  of  the  motor 
cell  at  b.  The  sensory  stimulus  arising  in  the  skin,  Z>',  is  transmitted  by  the  neuron 
dDce  to  /,  where  it  is  communicated  to  the  neuron  fg.  The  point  /  may  be  in  the  cord 
or  in  the  medulla  oblongata. 

In  order  to  understand  the  origin  of  the  anterior  spinal  nerve- 
roots  we  must  first  consider  the  course  of  the  centrifugal  neurites  in 
the  pyramidal  tracts  (Figs.  218,  219,  220).  These  enter  the  gray 
matter  and  end  in  teleneurites,  which  are  associated  with  the  tele- 


THE  CENTRAL  NERVOUS  SYSTEM.  243 

dendrites  of  the  cells  in  the  anterior  horn,  especially  those  which 
give  off  neurites  to  the  anterior  roots  of  the  spinal  nerves  (Fig. 
221,  j). 

The  foregoing  details  may  be  summarized  by  means  of  the  accom- 
panying diagram  (Fig.  225),  in  which  the  course  of  a  nervous  stim- 
ulus is  traced  from  the  organ  of  sense  in,  e.  g.,  the  skin,  to  the 
cortex  of  the  cerebrum,  where  it  is  translated  into  a  nervous  im- 
pulse, the  course  of  which  is  traced  to  the  motor  plates  of  the  vol- 
untary muscles.  The  reflex  mechanism  which  might  at  the  same  time 
be  set  into  operation  is  not  represented  in  the  diagram,  but  will  be 
sufficiently  obvious  from  an  inspection  of  Fig.  223.  It  will  be 
noticed  in  Fig.  225  that  both  the  sensory  stimulus  and  the  motor 
impulse  are  obliged  to  pass  through  at  least  two  neurons  before  they 
reach  the  ends  of  their  journeys.  But  the  nervous  currents  are  by 
no  means  entirely  confined  to  the  course  marked  by  the  arrows. 
Impulses  may  be  transmitted  in  an  incalculable  number  of  delicate 
tracts  through  the  collaterals  given  off  from  the  neurites  within  the 
central  nervous  system,  some  of  which  are  indicated  in  the  diagram, 
and  all  of  which  end  in  teleneurites  associated  with  the  teledendrites 
of,  perhaps,  several  neurons.  One  of  these  collateral  tracts  has 
already  been  considered,  namely  the  senso-motory  reflexes  illus- 
trated in  Fig.  223. 

II.   THE  CEREBELLUM. 

The  cerebellum  is  subdivided  into  a  number  of  laminae  by  deep 
primary  and  shallow  secondary  fissures.  The  gray  matter  of  the 
organ  occupies  the  surfaces  of  these  laminse,  while  their  central  por- 
tions are  composed  of  white  matter.  The  gray  matter  may  be 
divided  into  two  layers:  an  external  or  superficial  " molecular 
layer"  and  an  inner  " granular  layer"  (Figs.  226  and  227). 

The  molecular  layer  contains  two  forms  of  nerve-cells :  first,  the 
large  cells  of  Purkinje ;  second,  small  stellate  cells. 

The  cells  of  Purkinje  have  large,  oval,  or  pear-shaped  bodies  lying 
at  the  deep  margin  of  the  molecular  layer.  Their  dendrites  form 
an  intricate  arborescent  system  of  branches  extending  peripherally 
to  the  surface  of  the  gray  matter,  and  give  off  innumerable  small 
teledendrites  throughout  their  course.  All  these  branches  lie  in  one 
place,  perpendicular  to  the  long  axis  of  the  lamina  in  which  they 
are  situated,  and  the  teledendrites  come  into  relations  with  certain 
longitudinal  neurites  springing  from  the  cells  of  the  granular  layer, 


244 


NORMAL  HISTOLOGY. 


to  be  presently  described.  The  neurites  of  the  cells  of  Purkinje 
extend  through  the  granular  layer  into  the  white  matter  and  soon 
acquire  medullary  sheaths  (Fig.  226,  o) ;  but  before  they  leave  the 
granular  layer  they  give  off  collaterals,  which  re-ascend  into  the 
molecular  layer,  where  their  teleneurites  are  in  relations  with  the 

FIG.  226. 


Section  of  a  cerebellar  lamina  perpendicular  to  its  axis.  (R.  y  Cajal.)  ^4,  molecular  layer 
of  the  gray  matter ;  B,  granular  layer ;  C,  white  substance  ;  a,  cell  of  Purkinje ;  o,  its 
neurite,  giving  off  two  recurrent  collaterals  ;  b,  b,  stellate  cells  of  the  molecular  layer;  d, 
basket-like  distribution  of  the  teleneurites  of  one  of  their  collaterals  around  the  body 
of  a  cell  of  Purkinje ;  e,  superficial  stellate  cell,  which  does  not  appear  to  come  into  rela- 
tions with  the  bodies  of  the  cells  of  Purkinje,  but  must  lie  close  to  their  dendrites  ;  /, 
large  stellate  cell  of  the  granular  layer;  g,  small  stellate  cell  of  the  granular  layer;  h, 
centripetal  neurite  of  a  "  moss  "  fibre ;  n,  centripetal  neurite  distributed  in  the  molecular 
layer;  j,m,  neuroglia-cells.  The  arborescent  dendrites  of  only  one  of  the  cells  of  Pur- 
kinje are  represented  in  the  figure.  Were  those  of  the  neighboring  cells  also  represented, 
the  molecular  layer  of  the  gray  matter  would  display  an  enormously  complex  interdigi- 
tation.  of  such  filaments. 

teledendrites  of  neighboring  cells  of  Purkinje.  These  collaterals  are 
believed  to  occasion  a  certain  co-ordination  in  the  action  of  those 
cells  of  Purkinje  which  are  near  each  other. 

The  stellate  cells  of  the  molecular  layer  (Fig.  226,  6,  e)  pos- 


THE  CENTRAL  NERVOUS  SYSTEM. 


245 


sess  neurites,  which  lie  in  the  same  plane  with  the  arborescent 
dendrites  of  the  cells  of  Purkinje,  and  send  collaterals  to  end  in  a 
basket-work  of  teleneurites  applied  to  the  bodies  of  the  cells  of 
Purkinje.  The  terminal  teleneurites  of  these  stellate  cells  also  end 
in  the  same  situation.  Other  smaller  collaterals  extend  toward  the 
surface  of  the  cerebellar  lamina. 

The  granular  layer  of  the  gray  matter  also  contains  two  varieties 
of  nerve-cells  :  the  "  small  stellate  cells,"  which  are  most  numerous, 
and  the  u  large  stellate  cells." 

FIG.  227.     * 


Section  of  a  cerebellar  lamina  parallel  to  its  axis.  (R.  y  Cajal.)  A,  molecular  layer  of  the 
gray  matter ;  B,  granular  layer ;  C,  white  substance ;  a,  small  stellate  cell  of  the  granular 
layer,  from  which  a  neurite  enters  the  molecular  layer,  where  it  bifurcates,  sending 
branches  throughout  the  length  of  the  lamina ;  6,  bifurcation  of  one  of  these  neurites ; 
e,  slightly  bulbous  termination  of  one  of  the  neuritic  branches ;  d,  body  of  a  cell  of  Pur- 
kinje seen  in  profile ;  /,  neurite  of  a  cell  of  Purkinje. 

The  small  stellate  cells  (Fig.  226,  g,  and  Fig.  227,  a)  are  scat- 
tered throughout  the  granular  layer,  and  it  is  owing  to  the  abun- 
dance of  their  nuclei  that  this  layer  has  received  that  name.  Their 
dendrites  are  few  in  number  and  short,  but  their  neurites  are  very 
long.  They  extend  perpendicularly  into  the  molecular  layer,  where 
they  bifurcate,  the  branches  lying  parallel  with  the  axis  of  the 
cerebellar  lamina  and  its  surface.  These  fibres  appear  to  run  the 
whole  length  of  the  lamina,  and  to  come  in  contact  with  the  tele- 
dendrites  of  the  cells  of  Purkinje,  to  the  planes  of  which  they  run 
perpendicularly.  They  are  thought  to  coordinate  the  action  of  a 
long  series  of  the  cells  of  Purkinje. 


246  NORMAL  HISTOLOGY. 

The  large  stellate  cells  of  the  granular  layer  lie  near  its  external 
margin,  whence  they  send  their  dendrites  into  a  large  area  of  the 
molecular  layer,  while  their  neurites  are  distributed  in  the  granular 
layer,  where  they  must  come  into  relations  with  the  dendrites  of  the 
small  stellate  cells  (Fig.  226,  /). 

The  distribution  of  the  cells  and  their  processes  in  the  cerebellum 
indicates  a  very  complex  interchange  of  nervous  impulses  and  an 
extraordinary  coordination  in  the  action  of  the  various  neurons. 

This  complication  is  still  further  increased  by  the  presence  of 
centripetal  nenrites,  which 'enter  the  cerebellum  through  the  white 
matter  and  are  distributed  in  the  gray  matter.  These  are  of  two 
sorts :  first,  neurites  which  penetrate  the  granular  layer  and  are 
distributed  among  the  proximal  dendrites  of  the  cells  of  Purkinje 
(Fig.  226,  n) ;  second,  neurites,  called  "  moss  "  fibres,  which  are  dis- 
tributed among  the  cells  of  the  granular  layer.  The  teleneurites  of 
these  fibres  have  a  mossy  appearance,  whence  the  name  (Fig.  226,  h). 
The  origin  of  these  centripetal  neurites  is  not  known,  but  it  is  sur- 
mised that  the  "moss"  fibres  may  enter  the  cerebellum  through  the 
direct  cerebellar  tracts  of  the  cord. 

III.   THE  CEREBRUM. 

The  gray  matter  of  the  cerebral  cortex  has  been  divided  into  four 
layers  :  first,  an  external  molecular  layer ;  second,  the  layer  of 
small  pyramidal  cells;  third,  the  layer  of  large  pyramidal  cells; 
and,  fourth,  an  internal  layer  of  irregular  or  stellate  cells.  Of 
these  layers,  the  second  and  third  are  not  clearly  distinguishable 
from  each  other  (Fig.  228). 

The  molecular  layer  contains  three  sorts  of  nerve-cells,  two  of 
which  are  closely  related  to  each  other,  differing  only  in  the  form 
of  the  cell-bodies,  which  are  small  in  both  varieties  (Fig.  229,  A, 
B,  and  C) ;  while  the  cell-bodies  of  the  third  variety  are  large  and 
polygonal  (Fig.  229,  D).  The  small  cells  (A,  B,  C,  Fig.  229)  pos- 
sess two  or  three  tapering  processes,  which  at  first  resemble  proto- 
plasmic processes,  but  soon  assume  the  characters  of  neurites  or  axis- 
cylinders.  These  neurons,  then,  resemble  the  type  depicted  in  Fig. 
217,  III.  Their  neurites  run  parallel  to  the  surface  of  the  convo- 
lution in  which  they  are  situated,  sending  off  numerous  perpen- 
dicular collaterals,  and  finally  end  in  teleneurites  within  the  molec- 
ular layer.  The  collateral  and  terminal  teleneurites  are  probably 
in  relations  with  the  dendrites  of  the  pyramidal  cells  of  the  under- 


THE  CENTRAL  NERVOUS  SYSTEM. 


247 


FIG.  228. 


lying  layers,  which  form  arborescent  expansions  in  the  molecular 
layer,  similar  to  those  of  the  cells  of  Purkinje  in  the  cerebellum, 
extending  to  the  surface  of  the  gray  matter. 

The  large  stellate  cells  of  the  molecular  layer  (Fig.  229,  D)  send 
their  dendrites  in  various  directions  into 
the  molecular  layer  and  the  layer  of 
small  pyramidal  cells  lying  beneath  it. 
The  neurite  is  distributed  in  the  molec- 
ular and  upper  portions  of  the  under- 
lying layers,  but  is  never  extended  into 
the  white  matter.  The  dendrites  of  these 
cells  come  into  relations  with  the  neurites 
of  the  other  cells  of  this  layer  and  with 
those  that  proceed  upward  from  some  of 
the  cells  in  the  deeper  layers. 

The  small  spindle-  and  stellate  cells 
(A,  B,  C,  Fig.  229)  are  considered  to  be 
the  autochthonous  cells  of  the  cerebral 
cortex — i.  e.,  the  cells  of  the  brain  in 
which  the  highest  order  of  nervous  im- 
pulses find  their  origin.  The  small 
spindle-shaped  cells,  with  their  peculiar 
neurites,  are  extremely  abundant  and 
fill  the  molecular  layer  with  a  mass 
of  interwoven  filaments. 

The  second  and  third  layers  of  the 
cerebral  gray  matter  are  characterized 
by  the  presence  of  pyramidal  nerve- 
cells  of  various  sizes,  the  smaller  being 
relatively  more  abundant  in  the  second 
layer  and  the  larger  in  the  third  layer.  From  the  apex  of  the  pyram- 
idal cell  a  stout,  "  primordial  "  dendrite  passes  vertically  into  the 
molecular  layer,  where,  as  well  as  during  its  course  to  the  molecular 
layer,  it  gives  off  numerous  branches,  and  finally  ends  in  a  brush  of 
teledendrites  extending  to  the  surface  of  the  gray  matter  (Fig.  230, 
A,  B).  Other  and  shorter  dendrites  are  given  off  from  the  body  of  the 
cell,  which  ramify  and  end  in  the  second,  third,  or  fourth  layer  of  the 
gray  matter.  The  neurites  from  the  bases  of  the  pyramidal  cells  pass 
vertically  downward  into  the  white  substance,  where  they  may 
bifurcate,  giving  axis-cylinders  to  two  nerve-fibres.  While  within 


Vertical  section  of  the  cerebral  cor- 
tex, showing  its  layers.  (R.  y 
Cajal.)  1,  molecular  layer ;  f , 
layer  of  the  small  pyramidal 
cells ;  3,  layer  of  the  large  pyram- 
idal cells;  U, layer  of  polymor- 
phic cells ;  5,  white  matter. 


248 


NORMAL  HISTOLOGY. 
FIG.  229. 


Cells  of  the  molecular  layer  of  the  cerebral  cortex.    (R.  y  Cajal.)    A,  C,  small  spindle-shaped 
cells  ;  B,  small  stellate  cell ;  D,  large  stellate  cell.    The  branches  marked  c  are  neurites. 


FIG.  230. 


FIG.  231, 


Fig.  230.— Diagrammatic  section  through  the  cerebral  cortex.  (R.  y  Cajal.)  A,  small  pyram- 
idal cell  in  the  second  layer ;  B,  two  large  pyramidal  cells  in  the  third  layer ;  C,  D,  poly- 
morphic cells  in  the  fourth  layer ;  E,  centripetal  neurite  from  distant  nerve-centres  ; 
F,  collaterals  from  the  white  substance ;  G,  bifurcation  of  a  neurite  in  the  white  sub- 
stance. The  arrows  indicate  the  centripetal  and  centrifugal  courses  of  nerve-impxilses, 
but  it  is  probable  that  centripetal  impulses  have  to  pass  through  other  neurons  (perhaps 
the  spindle-cells  of  the  molecular  layer)  before  they  are  translated  into  centrifugal  im- 
pulses. 

Fig.  231.— Cells  with  short  neurites  in  the  cerebral  cortex.  (R.  y  Cajal.)  A,  molecular  layer ; 
B,  white  substance ;  a,  cells  with  neurites,  which  speedily  divide  into  numerous  tele- 
neurites  in  the  neighborhood  of  the  cell  belonging  to  the  same  neuron ;  6,  cell  with  n 
neurite  extending  vertically  toward,  but  not  entering,  the  molecular  layer ;  c,  cell  with 
a  neurite  distributed  within  the  molecular  layer ;  d,  small  pyramidal  cell. 


THE  CENTRAL  NERVOUS  SYSTEM.  249 

the  gray  matter,  and  after  their  entrance  into  the  white  matter, 
these  neurites  give  off  collaterals,  which  branch  and  end  in  terminal 
bulbous  expansions  without  breaking  up  into  a  set  of  teleneurites. 

The  irregular  cells  of  the  fourth  layer  (Fig.  230,  C9  D)  do  not 
send  their  dendrites  into  the  molecular  layer,  but  distribute  them 
within  the  deeper  layers  of  the  gray  matter.  Their  neurities,  like 
those  of  the  pyramidal  cells,  enter  the  white  matter,  where  they 
may  or  may  not  bifurcate. 

Besides  the  cells  in  the  deeper  layers  of  the  gray  matter  hitherto 
described,  those  layers  contain  cells  with  short  neurites,  which  are 
divisible  into  two  classes :  first,  spindle-shaped  or  stellate  cells, 
sending  their  neurites  into  the  molecular  layer  (Fig.  231,  c)  or  into 
the  second  layer  of  the  gray  matter  (Fig.  231,  6) ;  second,  poly- 
morphic cells  with  radiating  dendrites  and  copiously  branching 
neurites,  both  of  which  are  distributed  within  a  short  distance  of  the 
cell.  These  cells  are  believed  to  distribute  nervous  impulses  to  the 
neurons  in  their  vicinity. 

The  gray  matter  of  the  cortex  also  receives  centripetal  neurites 
from  the  white  matter,  which  give  off  numerous  collaterals  and  ter- 
minate in  the  molecular  layer. 

The  white  matter  of  the  cerebrum  contains  fibres  that  may  be 
divided  into  four  groups  :  first,  centrifugal  or  "  projection  "  fibres ; 
second,  "  commissure-fibres,"  which  bring  the  two  sides  of  the  brain 
into  coordination  (these  lie  in  the  corpus  callosum  and  in  the  ante- 
rior commissure) ;  third,  "  association-fibres,"  which  coordinate  the 
different  regions  of  the  cerebral  cortex  on  the  same  side ;  fourth, 
centripetal  fibres,  reaching  the  cortex  from  the  peripheral  nervous 
system  or  cord. 

The  centrifugal  or  projection-fibres  arise  from  all  parts  of  the 
cortex,  springing  from  the  pyramidal  and,  perhaps,  also  from  the 
irregular  cells.  Many  of  these  fibres  give  off  a  collateral,  which 
passes  into  the  corpus  callosum,  to  be  distributed  in  the  cortex  of 
the  opposite  side,  commissural  collaterals,  and  then  pass  on  to  the 
corpus  striatum,  to  the  gray  matter  of  which  further  collaterals 
may  be  given  off,  after  which  the  main  neurite  probably  passes  into 
the  pyramidal  tracts  of  the  cord  through  the  cerebral  crus  (Fig. 
232,  a). 

The  commissure-fibres  (Fig.  232,  6,  c)  also  arise  from  the  pyram- 
idal cells  of  the  cortex,  mostly  from  the  smaller  variety,  and  pass 
into  the  corpus  callosum  or  the  anterior  commissure,  to  be  dis- 


250 


NORMAL  HISTOLOGY. 


tributed  in  the  gray  matter  of  the  cortex  of  the  opposite  hemisphere, 
but  not  necessarily  to  the  corresponding  region.    These  commissural 


FIG.  232. 


Centrifugal  and  commissural  fibres  of  the  cerebrum.  (R.  y  Cajal.)  A,  corpus  callosum  ;  B, 
anterior  commissure ;  C,  pyramidal  tract ;  a,  large  pyramidal  cell,  with  a  neurite  sending 
a  large  collateral  into  the  corpus  callosum  and  then  entering  the  pyramidal  tract. 
Between  a  and  6  is  a  second  similar  cell,  the  neurite  from  which  contributes  no  branch 
to  the  corpus  callosum.  6,  small  pyramidal  cell  giving  rise  to  a  commissural  neurite  ;  c,  a 
similar  cell,  the  neurite  of  which  divides  into  a  commissural  and  an  association  branch  ; 
d,  collateral  entering  the  gray  matter  of  the  opposite  hemisphere  ;  e,  terminal  teleneu- 
rites  of  a  commissural  fibre. 

fibres  give  off  collaterals,  which  also  end  in  the  gray  matter,  and 
are  accompanied  by  collaterals  from  the  centrifugal  fibres,  which 
likewise  end  in,  and  send  collaterals  to,  the  gray  matter. 

FIG.  233. 


Association-fibres  of  the  cerebrum.  (R.  y  Cajal.)  The  figure  represents,  diagrammatically, 
a  sagittal  section  through  one  of  the  cerebral  hemispheres,  a,  pyramidal  cell,  with  neu- 
rite giving  off  collaterals  to,  and  ending  in,  the  gray  matter  of  the  same  side ;  b,  a  similar 
cell ;  c,  cell  with  a  branching  neurite  passing  to  different  parts  of  the  hemisphere ;  d, 
teleneurites ;  e,  terminal  collateral  twigs. 


The  origin,  course,  and  general  distribution  of  the  association- 
fibres  are  indicated  in  Fig.  233.     They  are  so  numerous  that  they 


THE  CENTRAL  NERVOUS  SYSTEM.  251 

form  the  great  bulk  of  the  white  substance,  where  they  are  inex- 
tricably interwoven  with  the  other  fibres  there  present. 

Besides  the  centripetal  neurites  of  the  association  and  commissural 
neurons,  their  collaterals  and  those  of  the  projection-fibres,  the  gray 
matter  of  the  cortex  receives  terminal  neurites  from  larger  fibres 
that  are  probably  derived  from  the  cerebellum  and  cord  (Fig.  230, 
E).  These  give  off  numerous  collaterals  and  teleneurites,  which  are 
distributed  to  the  small  pyramidal  cells  of  the  second  layer,  and 
probably  also  penetrate  into  the  molecular  layer,  where  they  end  in 
numerous  teleneurites  among  the  cells  of  that  layer. 

In  the  diagrammatic  figure  230  the  probable  course  of  nervous 
stimuli  to  and  from  the  cerebral  cortex  is  indicated.  The  possi- 
bilities of  transmission  within  a  structure  of  such  marvellous  com- 
plexity are  incalculable. 

The  above  structural  details  of  the  central  nervous  system  are 
chiefly  taken  from  the  publications  of  Ramon  y  Cajal.  They  are 
the  result  of  researches  carried  on  by  the  application  of  the  methods 
devised  by  Golgi  to  the  nervous  structures  of  the  lower  vertebrates 
and  embryos.  Such  details  cannot  be  observed  when  specimens 
have  been  hardened  and  stained  by  methods  used  for  the  study  of 
other  structures.  In  such  specimens  the  nuclei  of  the  nerve-cells 
and  those  of  the  neuroglia  are  stained  and  become  prominent.  But 
the  multitude  of  nervous  filaments  lying  between  the  cells  and  the 
processes  of  the  neuroglia-cells  are  not  differentiated,  but  appear 
as  an  indefinite,  finely  granular  material,  in  which  the  cell-bodies 
apparently  lie.  Where  the  cells  are  sparse  or  small,  as  in  the  first 
layer  of  the  cerebral  gray  matter,  the  tissue  appears  finely  molecu- 
lar. Where  the  cells  are  numerous  but  small,  their  stained  nuclei 
give  the  tissue  a  granular  appearance,  as,  for  example,  in  the  second 
layer  of  the  cerebellar  cortex. 

The  brain  and  spinal  cord  are  invested  by  a  membrane  of  areolar 
tissue,  called  the  "pia  mater."  Extensions  of  this  areolar  tissue 
penetrate  the  substance  of  the  cord  and  brain,  giving  support  to 
bloodvessels  and  their  accompanying  lymphatics.  This  areolar 
tissue  also  extends  into  the  ventricles  of  the  brain,  where  it  receives 
an  external  covering  of  epithelium  continuous  with  that  lining  the 
ventricles,  which  is  ciliated.  Externally,  the  areolar  tissue  is  con- 
densed to  form  a  thin  superficial  layer. 


CHAPTER  XIX. 
THE  ORGANS  OF  THE  SPECIAL  SENSES. 

1.  Touch. — The  nervous  filaments  distributed  among  the  cells 
of  stratified  epithelium  have  already  been  depicted  in  Fig.  93. 
Similar  filaments  occur  in  the  human  epidermis,  and  it  is  probable 
that  some  of  them  are  the  teledendrites  of  spinal  ganglion-cells, 
while  others  are  centrifugal  teleneurites  subserving  the  functions 


FIG.  234. 


FIG.  235. 


Tactile  corpuscles. 
Fig.  234.— Meissner's  corpuscle,  from  the  human  corium.    (Bohm  and  Davidoff.)    a,  upper 

portion,  in  which  the  epithelial  cells  alone  are  represented.    The  nuclei  of  those  cells 

are  in  the  broader  peripheral  portion  of  the  cytoplasm ;  6,  nerve-dendrite  coiled  about 

the  epithelial  cells ;  c,  nerve-fibre. 
Fig.  235. — Krause's  corpuscle,   from   the   human   conjunctiva.      (Dogiel.)     a,  endothelial 

envelope ;  6,  nucleus  of  connective-tissue  cell  within  the  fibrous  capsule  ;  c,  nerve-fibre. 

of  nutrition,  etc.,  or  the  teledendrons  of  neurons  belonging  to  other 
than  the  spinal  system  of  nerves. 

Besides   these   nervous  terminations  the  skin  possesses  certain 
bodies,  which  are  called  "  tactile  corpuscles  "  and  "  Pacinian  bodies." 

252 


THE  ORGANS  OF  THE  SPECIAL  SFJNSES.  253 

These  are  situated  in  the  corium,  the  former  lying  in  some  of  the 
papillae  projecting  into  the  rete  mucosum. 

The  tactile  corpuscles  are  of  two  forms,  differing  slightly  from 
each  other  in  structure  :  first,  those  of  Meissner,  and,  second,  those 
of  Krause. 

The  tactile  corpuscles  of  Meissner  (Fig.  234)  consist  of  a  group 
of  epithelial  cells  closely  associated  with  the  teledendrites  of  a 
nerve-fibre.  The  cells  are  closely  compacted  together  to  form  an 
ellipsoid  body.  The  nervous  dendrite,  with  its  medullary  sheath, 
enters  this  body  at  one  of  its  ends,  and,  after  making  one  or  two 
spiral  turns  around  the  mass  of  epithelial  cells,  loses  its  medullary 
sheath  and  breaks  up  into  a  number  of  teledendrons,  which  are  dis- 
tributed among  the  epithelial  cells.  The  neurilemma  and  the 
endoneurium  of  the  fibre  are  continued  over  the  corpuscle,  consti- 
tuting a  species  of  capsule. 

The  tactile  corpuscles  of  Krause  (Fig.  235)  possess  a  capsule 
composed  of  delicate  fibrous  tissue,  covered  and  lined  with  endo- 
thelial  cells.  The  dendrite  of  the  nerve-fibre  loses  its  medullary 
sheath  upon  penetrating  this  capsule,  and  then  breaks  up  into  tele- 
dendrites. that  form  a  complex  tangle  within  the  cavity  of  the  cor- 
puscle. There  appear  to  be  no  cells  among  the  teledendrites,  the 
interstices  being  occupied  by  lymph.  These  corpuscles  are  espe- 
cially abundant  in  the  conjunctiva  and  the  edges  of  the  eyelids, 
but  occur  also  in  the  lip,  large  intestine,  posterior  surface  of  the 
epiglottis,  and  the  glans  penis  and  clitoris.  They  may  receive 
dendrites  from  more  than  one  nerve.  Those  of  Meissner  are  found 
throughout  the  skin,  being  most  abundant  where  the  tactile  sense  is 
most  acute. 

The  Pacinian  corpuscles  (Fig.  236)  are  large  oval  bodies,  com- 
posed of  a  number  of  concentric  cellular  lamellae,  surrounding  a 
central,  almost  cylindrical  cavity,  and  covered  externally  with  a 
layer  of  endothelioid  cells,  which  appear  to  be  continuous  with  the 
delicate  endoneurium  of  the  fibre.  The  latter  enters  the  corpuscle 
at  one  of  its  ends,  soon  loses  its  medullary  sheath,  and  is  finally 
subdivided  into  a  number  of  teledendrites  within  the  central  cavity. 

The  "genital  corpuscles"  which  are  found  in  the  glans  of  the 
penis  and  that  of  the  clitoris  are  similar  in  structure  to  the  Pacinian 
corpuscles,  but  the  lamellar  envelope  of  the  latter  is  here  reduced  to 
one  or  two  ill-developed  lamellae. 

The   nervous  impulses  inaugurated  in  the  tactile  and  Pacinian 


254 


NORMAL  HISTOLOGY. 


corpuscles  are  probably  transmitted  to  the  sensorium  in  the  manner 
indicated  in  Fig.  225. 

Pacinian  corpuscles  are  found  in  the  palms  and  soles,  on  the 
nerves  of  the  joints  and  periosteum,  in  the  pericardium,  and  in  the 
pancreas. 

2.  Taste. — The  special  organs  of  taste  appear  to  be  the  taste- 

FIG.  236. 


Pacinian  corpuscle,  from  the  mesentery  of  the  cat.  (Klein.)  a,  nerve-fibre ;  6,  concentric 
capsule.  The  nature  of  the  cells  in  this  capsule  is  a  matter  of  doubt ;  analogy  would 
suggest  their  epithelial  nature. 

buds,  situated  in  the  walls  of  the  sulci  surrounding  the  circum- 
vallate  papillae  of  the  tongue  (see  Fig.  109). 

The  taste-buds  are  bulb-shaped  groups  of  epithelial  and  nervous 
cells,  situated  within  the  stratified  epithelium  lining  the  sulci.  The 
cells  composing  these  buds  are  spindle-shaped  or  tapering,  and  their 
ends  are  grouped  together  at  the  base  of  the  bud  and  converge  at 
its  apex,  where  they  occupy  a  "  pore  "  in  the  stratified  epithelium. 
The  epithelial  cells  do  not  appear  to  be  active  in  the  inauguration 
of  nervous  impulses,  but  the  more  spindle-shaped  cells  lying  among 
them  seem  to  be  endowed  with  nervous  functions.  They  may,  pos- 
sibly, be  regarded  as  peculiar  neurons ;  their  distal  processes,  which 
receive  stimuli  at  the  pore,  being  the  dendrite,  while  the  proximal 
process  is  the  neurite.  The  latter  divides  into  a  number  of  minute 
branches,  which,  from  this  point  of  view,  might  be  regarded  as  tele- 
neurites.  Be  this  as  it  may,  these  branches  come  into  close  relations 


THE  ORGANS   OF  THE  SPECIAL  SENSES.  255 

with  the  teledendrites  of  nerve-fibres  supplied  to  the  taste-bud 
(Fig.  237).  The  stratified  epithelium  surrounding  the  taste-buds, 
as  elsewhere,  contains  teledendrites  from  sensory  nerves. 

3.  Smell. — The  olfactory  organ  occupies  a  small  area  at  the  top 
of  the  nasal  vault,  and  extends  for  a  short  distance  upon  the  sep- 
tum and  external  wall.  Its  exposed  surface  is  about  equal  to  that 

FIG.  237. 


Diagram  of  a  taste-bud  and  its  nervous  supply.  (Dogiel.)  a,  radicle  of  the  gustatory  nerve  ; 
b,  radicle  of  a  sensory  nerve  ;  c,  epithelial  cell ;  d,  nerve-cell.  The  shaded  part  of  the 
figure  represents  the  stratified  epithelium  lining  the  sulcus  of  the  circumvallate  papilla. 
Only  one  of  the  epithelial  or  supporting  cells  of  the  upper  bud  is  represented  in  the 
figure ;  the  others  are  omitted.  The  structure  of  the  lower  bud  is  not  shown. 

of  a  five-cent  piece.  It  is  a  modified  portion  of  the  mucous  mem- 
brane of  the  nose,  which  may  be  divided  into  this,  the  olfactory 
portion,  and  the  general  or  respiratory  portion. 

The  respiratory  portion  of  the  nasal  mucous  membrane  is  covered 
with  a  stratified,  columnar,  ciliated  epithelium,  with  occasional 
mucigenous  goblet-cells,  resting  upon  a  basement-membrane.  Be- 
neath this  is  the  membrana  propria,  resembling  that  of  the  small 
intestine  in  being  rich  in  lymphadenoid  tissue,  which  may,  here  and 
there,  be  condensed  into  solitary  follicles.  Beneath  the  membrana 
propria  is  a  richly  vascularized  submucous  areolar  tissue,  containing 
compound  tubular  glands,  the  glands  of  Bowman,  which  open  upon 
the  surface  of  the  mucous  membrane.  These  glands  secrete  both 
mucus  and  a  serous  fluid. 

In  the  olfactory  region  the  columnar  epithelial  cells  are  devoid  of 
cilia,  but  possess  a  thin  cuticle,  and  the  epithelium  rests  directly 
upon  the  lymphadenoid  tissue,  without  the  intermediation  of  a  base- 
ment-membrane (Fig.  238).  Between  these  epithelial  cells  are  the 


256 


NORMAL  HISTOLOGY. 


nervous  cells,  which  constitute  the  receptive  elements  of  the  olfac- 
tory nervous  tract.  These  are  cells  with  large  nuclei  and  cylin- 
drical distal  bodies,  which  terminate  at  the  surface  of  the  epithelial 
layer  in  several  delicate  hairs  projecting  from  the  surface  (Figs.  239 
and  240).  The  proximal  ends  of  the  cells  rapidly  taper  to  a  delicate 

FIG.  238. 


Bt 

Vertical  section  through  the  olfactory  mucous  membrane  of  the  human  nose.  (Brunn.) 
ez,  nuclei  of  the  columnar  epithelial  cells ;  rz,  nuclei  of  the  nervous  or  olfactory  cells 
lying  among  those  of  the  epithelium ;  bz,  nuclei  of  basal  pyramidal  epithelial  cells  lying 
among  the  branching  proximal  ends  of  the  columnar  epithelial  cells  and  tapering  ends  of 
the  nervous  cells ;  pzt  pigmented  cell  in  the  layer  of  lymphadenoid  tissues  beneath  the 
epithelium ;  Ba,  duct  of  a  gland  of  Bowman;  Bb,  dilated  subepithelial  portion  of  the 
duct,  receiving  several  of  the  tubular  acini,  Bt.  The  connection  between  the  duct  and 
tubes  is  not  shown,  n,  n,  branches  of  the  olfactory  nerve ;  rz*,  atypical  nervous  cell. 

filament,  which  extends  through  the  subepithelial  tissue  and  becomes 
associated  with  others  to  form  the  olfactory  nerve.  The  distal  ends 
of  the  nerve-cells  represent  the  dendrites  of  neurons,  the  neurites  of 
which  form  the  axis-cylinders  in  the  olfactory  nerve. 

The  neurites  in  the  olfactory  nerve  pass  through  the  cribriform 
plate  of  the  ethmoid  bone  to  the  olfactory  bulb  of  the  brain,  where. 


THE  ORGANS  OF  THE  SPECIAL  SENSES. 
FIG.  239. 


257 


Epithelial  layer  of  the  human  olfactory  mucous  membrane.  (Brunn.)  Isolated  elements. 
Three  epithelial  cells,  with  forked  proximal  ends,  are  represented,  together  with  a  ner- 
vous cell  bent  out  of  position  and  the  distal  end  of  a  second  nervous  cell.  M.I,  cuticle 
of  the  columnar  epithelium,  which  is  not  continued  over  the  end  of  the  nervous  cell. 
The  cuticle  of  neighboring  cells  unites  at  the  edges  to  form  a  species  of  membrane,  which 
appears  to  be  perforated  for  the  exit  of  the  distal  ends  of  the  nervous  cells.  A  similar 
cuticle  is  found  in  the  retina,  where  it  has  received  the  name  "  limiting  membrane." 

FIG.  240. 


Vertical  section  of  the  epithelium,  showing  the  arrangements  of  its  elements.    The  nervous 
cells,  with  their  neurites,  are  black. 

they  terminate  in  teleneurites  within  little  globular  structures,  called 
the  "  glomeruli  of  the  bulb." 


17 


258  NORMAL  HISTOLOGY. 

The  olfactory  bulb  may  be  divided  into  five  layers :  first,  the 
layer  of  peripheral  nerves,  containing  the  neurites  of  the  olfactory 
nerve ;  second,  the  layer  containing  the  olfactory  glomeruli ;  third, 
the  molecular  layer ;  fourth,  the  layer  of  the  mitral  cells  ;  fifth,  the 
granular  layer. 

The  first  layer  is,  as  already  stated,  occupied  by  the  neurites  from 
the  nervous  cells  in  the  olfactory  mucous  membrane.  These  neurites 
constitute  the  axis-cylinders  of  the  olfactory  nerve. 

The  glomeruli  of  the  second  layer  are  small  globular  masses 
formed  by  the  closely  associated  teleneurites  of  the  olfactory  nerves 
and  teledendrites  from  the  mitral  ceils  of  the  fourth  layer,  the  den- 
drites  from  which  pass  through  the  third  or  molecular  layer.  A 
few  cells  of  neurogliar  nature  may  be  associated  with  these  nervous 
terminations,  but  the  chief  mass  of  each  glomerulus  is  composed  of 
interwoven  teleneurites  and  teledendrites. 

The  third,  or  molecular,  layer  contains  small  spindle-shaped 
nerve-cells,  which  send  dendrites  to  the  glomeruli  of  the  second 
layer  and  neurites  into  the  granular  (fifth)  layer,  where  they  turn 
and  take  a  centripetal  direction  toward  the  cerebrum. 

The  fourth  layer  is  characterized  by  the  presence  of  large  tri- 
angular nerve-cells,  the  mitral  cells,  the  dendrites  from  which  pass 
through  the  molecular  layer,  to  end  in  teledendrites  within  the 
glomeruli.  A  single  mitral  cell  sends  dendrites  to  more  than  one 
glomerulus.  The  neurites  from  these  cells  pass,  centripetally,  to 
the  olfactory  centre  of  the  cerebrum. 

The  fifth,  granular,  layer  contains  the  centripetal  neurites  of  the 
mitral  cells,  and  also  centrifugal  neurites  from  the  cerebrum.  The 
latter  are  distributed  in  teleneurites  within  the  granular  layer 
itself.  This  layer  also  contains  small  polygonal  nerve-cells  of  two 
sorts  :  first,  cells  resembling  those  of  the  third  type  represented  in 
Fig.  217,  the  processes  from  which  are  distributed  in  the  granular 
and  molecular  layers.  They  are  probably  association-cells.  Second, 
cells  (Fig.  241)  with  dendrites  in  the  granular  layer  and  teleneurites 
in  the  molecular  layer.  These  cells  would  distribute  impulses  re- 
ceived from  the  centrifugal  fibres,  which  end  in  the  granular  layer, 
among  the  teledendrites  in  the  molecular  layer. 

The  sense  of  smell,  then,  is  aroused  by  stimulations  of  the  distal 
ends  of  the  nervous  cells  in  the  olfactory  mucous  membrane  (Fig. 
241),  which  are  transmitted  to  the  glomeruli,  where  they  leave  the 
first  neuron,  being  communicated  to  the  second,  represented  by  the 


THE  ORGANS  OF  THE  SPECIAL  SENSES. 


259 


mitral  cells  and  their  processes,  by  which  they  are  conveyed  to  the 
cerebral  cortex.     In  its  passage  through  this  tract  numerous  collat- 


FIG.  241. 


Diagram  of  the  nervous  mechanism  of  the  olfactory  apparatus.  (R.  y  Cajal.)  a,  olfactory 
portion  of  the  nasal  mucous  membrane ;  6,  second  or  glomerular  layer  of  the  olfactory 
bulb  j,  at  the  right  edge  of  the  molecular  layer,  which  is  dotted.  The  cells  of  this  layer 
are  omitted,  c,  fourth  layer  of  the  bulb,  the  layer  of  the  mitral  cells,  two  of  which  are 
represented  ;  e,  m,  cells  of  the  fifth  or  granular  layer ;  d,  olfactory  tract ;  g,  cerebral  cor- 
tex ;  h,  neurite  from  a  mitral  cell,  giving  off  a  collateral  to  the  deudrites  of  a  pyramidal 
cell  in  the  gray  matter  of  the  brain ;  /,  pyramidal  cells  of  the  olfactory  tract ; .;',  collateral 
from  a  mitral  neurite  passing,  recurrently,  into  the  molecular  layer ;  I,  centrifugal  neurite 
from  the  cerebrum. 

eral  and  association-tracts  may  be  influenced  in  a  manner  too  com- 
plicated to  be  readily  followed. 

FIG.  242. 


Diagram  of  the  distribution  of  the  auditory  nerve  within  the  mucous  membrane  of  the  crista 
acustica.  (Niemack.)  The  bodies  of  the  hair-cells  are  dotted.  Between  them  are  the 
cells  of  Deiters,  the  nuclei  of  which  are  shown  below  the  hair-cells.  The  nervous  fila- 
ments are  distributed  between  these  cells. 

4.  Hearing. — The  acoustic  nervous  apparatus  resembles  somewhat 
that  which  subserves  the  sense  of  touch.  The  receptive  portion  consists 


260  NORMAL  HISTOLOGY. 

of  a  layer  of  epithelium  containing  two  sorts  of  cells :  first,  ciliated 
cells,  which  are  somewhat  flask-shaped  and  are  called  "  hair-cells  " ; 
second,  epithelial  cells,  the  "  cells  of  Deiters,"  which  surround  and 
enclose  the  hair-cells,  except  at  their  free  ends,  and  reach  the  sur- 
face of  the  mucous  membrane,  where  their  ends  are  cuticularized. 
These  cells  of  Deiters  extend  from  the  surface  of  the  membrane  to 
the  basement-membrane,  while  the  hair-cells  extend  only  for  a  por- 
tion of  that  distance. 

The  dendrites  of  the  auditory  nerve  are  distributed  among  these 
cells,  but  are  not  in  organic  union  with  them  (Fig.  242).  In  this 
respect  the  auditory  apparatus  diifers  from  the  olfactory  and  resem- 
bles the  tactile.  The  nervous  dendrites  are  processes  of  bipolar 
ganglion-cells  situated  in  the  ganglia  on  the  branches  of  the  auditory 
nerve.  The  neurites  from  those  cells  presumably  carry  the  nervous 
stimuli  to  the  cerebrum.  The  bipolar  cells  are,  therefore,  analogous 
to  the  posterior  root  ganglion-cells  of  the  spinal  nerves.  Whether 
this  single  neuron  carries  the  nervous  stimulus  directly  to  the  cere- 
bral cortex  cannot  be  stated,  but  it  is  probable  that  there  is  an  inter- 
mediate neuron  in  the  tract  of  transmission,  perhaps  in  the  medulla 
oblongata. 

5.  Sight. — The  receptive  nervous  organ  of  vision  is  the  retina. 
This  has  an  extremely  complicated  structure,  which  may  be  divided 
into  the  following  nine  layers  : 

1.  The  layer  of  pigmented  epithelium,  which  lies  next  to  the 
choroid  coat  of  the  eye,  and  is,  therefore,  the  most  deeply  situated 
coat  of  the  retina ;  2,  the  layer  of  rods  and  cones ;  3,  the  external 
limiting  membrane ;  4,  the  outer  granular  layer ;  5,  the  outer  molec- 
ular layer ;  6,  the  inner  granular  layer ;  7,  the  inner  molecular 
layer ;  8,  the  ganglionic  layer ;  9,  the  layer  of  nerve-fibres. 

Internal  to  the  ninth  layer  is  the  internal  limiting  membrane, 
which  separates  the  retinal  structures  from  the  vitreous  humor 
occupying  the  cavity  of  the  eyeball.  The  general  character  and 
associations  of  these  layers  are  shown  in  Fig.  243. 

1.  The  layer  of  pigmented  epithelium  is  made  up  of  hexagonal 
cells,  which  are  separated  from  each  other  by  a  homogeneous 
cement  and  form  a  single  continuous  layer  upon  the  external  sur- 
face of  the  retina.  They  are  in  contact  with  the  rods  and  cones 
of  the  next  layer,  and  send  filamentous  prolongations  between  those 
structures.  The  pigment  lies  within  these  filamentous  processes 
and  the  portion  of  cytoplasm  continuous  with  them,  but  its  position 


THE  ORGANS  OF  THE  SPECIAL  SENSES. 


261 


varies  with  the  functional  activities  of  the  organ.  When  the  eye 
lias  been  exposed  to  light  the  pigment  is  found  lying  deeply  between 
the  rods.  When  the  eye  has  been  at  rest  for  some  time  the  pigment 
is  retracted  in  greater  or  less  degree  within  the  body  of  the  cell. 

2.  The  rods  and  cones  are  the  terminal  structures  of  cells  which 
extend  from  the  fifth  layer  to  the  first.     The  nuclei  of  these  cells 

FIG.  243. 


Diagram  of  the  retina.  (Kallius.)  I.,  pigmented  epithelial  layer;  II.,  layer  of  the  rods  and 
cones ;  III.,  external  limiting  membrane ;  IV.,  outer  granular  layer ;  V.,  outer  molecular 
layer;  VI.,  inner  granular  layer;  VII.,  inner  molecular  layer;  VIII.,  ganglionic  layer; 
IX.,  layer  of  nerve-fibres,  z,  pigmented  epithelial  cells ;  c,  at  the  bottom  of  the  external 
limiting  membrane,  rods ;  b,  cone  cells ;  c-h,  ganglion-cells  of  the  sixth  layer  connecting 
the  fourth  layer  with  the  eighth ;  i,  horizontal  cell  sending  a  process  into  the  seventh 
layer;  k-q,  " spongioblasts,"  or  neurons  of  the  third  type  (Fig.  217);  r-w,  ganglion-cells 
of  the  eighth  layer;  x,  sustentacular  cell  of  Miiller,  with  striated  upper  end  forming 
a  part  of  the  external  limiting  membrane ;  y,  y,  neuroglia-cells.  It  should  be  borne  in 
mind  that  in  sections  of  the  retina  numerous  elements  of  the  various  sorts  here  rep- 
resented are  crowded  together  to  form  a  compact  tissue.  The  centrifugal  fibres  which 
reach  the  retina  from  the  cerebrum  are  omitted  from  this  diagram.  They  are  distributed 
in  the  inner  granular  or  sixth  layer.  The  light  entering  the  eye  passes  through  the  layers 
represented  in  the  lower  part  of  this  figure  before  it  can  affect  the  rods  and  cones. 

lie  within  the  fourth  layer,  to  which  they  give  a  granular  appear- 
ance (Fig.  243). 

3.  The  external  limiting  membrane  is  formed  by  the  circularized 
outer  ends  of  certain  sustentacular  epithelial  cells,  the  "cells  of 


262  NORMAL  HISTOLOGY. 

Miiller"  (Fig.  243,  x),  which  extend  from  this  layer  to  the  in- 
ternal limiting  membrane  and  serve  to  support  the  various  elements 
of  the  retina.  The  nuclei  of  these  cells  lie  in  the  seventh  layer,  to 
the  granular  character  of  which  they  contribute.  The  portion  of 
the  cell  which  lies  in  the  fourth  layer  of  the  retina  is  indented 
with  numerous  oval  depressions  receiving  the  nuclei  of  the  cells 
carrying  the  rods  and  cones,  which  they  both  support  and  isolate 
from  each  other.  The  filamentous  cell-bodies  of  those  elements 
are  also  separated  by  the  cells  of  Miiller.  In  the  sixth  and  seventh 
layers  delicate  processes  from  these  cells  serve  a  similar  purpose, 
and  in  the  eighth  layer  their  deep  extremities  fork  to  give  support 
to  the  ganglion-cells.  Beyond  the  ninth  layer  the  ends  of  these 
forks  expand  and  come  in  contact  with  each  other  at  their  edges 
to  form  the  "  internal  limiting  membrane." 

4.  The  fourth,  or  outer  granular  layer  contains,  as  already  stated, 
the  nuclei  and  elongated  bodies  of  the  cells  that  carry  the  rods  and 
cones  of  the  second  layer.     The  bodies  of  the  former  are  almost 
filamentous  in  character,  but  expand  to  enclose  the  oval  nucleus, 
which    lies   at   various   depths   in  different   cells.     The   cell-body 
expands  again  near  the  external  limiting  membrane,  through  which 
it  passes  to  form  the  rod.     At  the  other  end  the  filamentous  cell- 
body  terminates  in  a  minute  knob  in  the  fifth  layer  of  the  retina. 
The  cells  which  form  the  cones  have  nuclei  lying  near  the  external 
limiting  membrane  and  cylindrical  bodies  terminating  in  a  brush 
of  filaments  in  the  fifth  layer. 

5.  The  outer  molecular  layer,  also  called  the  "  outer  plexiform 
layer,"  owes  its  appearance  to  a  multitude  of  filaments,  part  of  which 
have  been  described  as  the  terminations  of  the  cells  bearing  the  rods 
and  cones,  the  rest  being  the  terminations  of  nerve-processes  spring- 
ing from  the  cells  of  the  sixth  layer. 

6.  The  sixth  layer  has  a  granular  appearance,  because  of  the 
presence  within  it  of  the  cells  of  a  great  number  of  short  neurons. 
These  are  of  two  sorts :  first,  those  belonging  to  the  first  type,  rep- 
resented in  Fig.  217,  which  have  dendrites  in  relation  in  the  fifth 
layer  with  the  filaments  of  the  cells  bearing  the  rods  and  cones,  and 
neurites  that  come  into  relation  in  the  seventh  layer  with  the  den- 
drites of  ganglion-cells  lying  in  the  eighth  layer ;  second,  neurons 
of  the   third   type,  shown  in   Fig.  217,  which,  in   this   situation 
have  been  called  "  spongioblasts."     These,  which  we  may  regard 
as  association-neurons,   form  two  groups  :  first,  those  which   send 


THE  ORGANS  OF  THE  SPECIAL  SENSES. 


263 


processes  into  the  fifth  layer ;  and,  second,  those  which  send  their 
processes  into  the  seventh  layer ;  but,  aside  from  the  neurons  in- 
cluded in  these  two  groups,  there  are  certain  cells  (Fig.  243,  i) 
which  send  processes  into  both  the  fifth  and  the  seventh  layers. 

7.  The  seventh,  inner  molecular  or  "  inner  plexiform  "  layer  owes 
its  delicate  structure  to  the  fact  that  it  is  here  that  the  teleneurites  of 
the  cells  in  the  sixth  layer  come  into  relations  with  the  teledendrites 
of  the  ganglion-cells  of  the  eighth  layer. 

8.  The  eighth  layer  contains  those  ganglion-cells  whose  teleden- 
drites receive  impressions  from  the  teleneurites  derived  from  the 
sixth  layer,  and  send  their  neurites  into  the  optic  nerve.     These 
ueurites  form  the  chief  constituent  of  the  ninth  layer  of  the  retina. 

It  will  be  observed  in  Fig.  243  that  the  basal  expansions  of  the 
cells  bearing  the  cones  are  mostly  in  relation  with  the  teledendrites 
of  a  single  neuron  of  the  sixth  layer,  and  that  this  neuron  is,  again, 
in  close  relations  with  the  teledendrites  of  but  one  ganglion-cell  of 
the  eighth  layer.  This  arrangement  would  not  favor  a  diffusion  of 

FIG.  244. 


\ 


Diagram  of  the  nervous  mechanism  of  vision.  (R.  y  Cajal.)  A,  retina;  B,  optic  nerve;  C, 
corpus  geniculatum.  a,  cone ;  b,  rod ;  c,  d,  bipolar  nerve-cells  of  the  outer  granular  layer ; 
e,  ganglion-cell;  /,  centrifugal  teleneurites;  g,  "  spongioblast " ;  h,  teleneurites  from  optic 
nerve ;  j,  neuron  receiving  and  further  transmitting  the  nervous  impulse ;  r,  cell  trans- 
mitting the  centrifugal  impression.  The  courses  of  nervous  impressions  are  indicated 
by  the  arrows. 

the  impressions  inaugurated  in  the  cones.    The  arrangement  is  quite 
different  in  the  case  of  the  cells  bearing  the  rods. 

The  probable  course  of   nervous  impressions  to  and  from  the 
retinal  elements  is  represented  in  Fig.  244. 


PART  II. 

HISTOLOGY  OF  THE   MORBID 
PROCESSES. 


CHAPTER  XX. 
DEGENERATIONS  AND   INFILTRATIONS. 

As  the  result  of  disturbances  in  the  internal  economy  of  the  cell, 
a  variety  of  changes,  called  degenerations  or  infiltrations,  are  occa- 
sioned, some  of  which  are  accompanied  by  visible  alterations  in  the 
structure  of  the  cell  or  of  the  intercellular  substances.  We  are  so 
ignorant  of  the  exact  nature  of  the  normal  processes  carried  on  by 
the  cell  that  it  is  impossible  for  us  to  furnish  an  explanation  of  most 
of  these  changes  due  to  abnormal  conditions.  We  can  only  describe 
and  group  the  results  according  to  their  apparent  likenesses  until 
such  time  as  an  increased  knowledge  permits  a  more  enlightened 
conception  of  their  significance. 

The  degenerations  are  changes  in  which  one  of  the  results  is  the 
conversion  of  a  part  of  the  normal  structure  into  some  other  sub- 
stance. They  imply  a  loss  on  the  part  of  the  tissue-elements  suffer- 
ing  the  change. 

The  infiltrations  are  departures  from  the  normal  in  that  material 
from  without  is  deposited  either  within  or  between  the  tissue-ele- 
ments in  an  abnormal  form  or  degree.  They  imply  a  gain  of 
material,  but  not  necessarily  an  advantageous  gain,  on  the  part  of 
the  tissues  affected. 

Such  general  statements  of  an  obscure  subject  must  inevitably  be 
vague.  They  are  largely  based  upon  theoretical  considerations,  and 
it  becomes  difficult  in  many  cases  to  decide  definitely  whether  a 
given  condition  is  due  to  degenerative  changes  or  is  the  result  of 
infiltration,  or  whether  both  processes  may  not  have  contributed 
toward  producing  the  abnormal  appearances  which  are  observed. 

265 


266  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

It  must  be  borne  in  mind  that  changes  which  are  morbid  in  a 
given  part  of  the  body  may  be  included  in  perfectly  normal  proc- 
esses carried  on  in  other  parts,  and  are,  therefore,  not  beyond  the 
pale  of  possible  normal  cellular  activity.  In  fact,  most  of  the 
morbid  processes  observed  find  parallels  in  the  physiological  activ- 
ities of  some  portion  of  the  body. 

In  bone,  for  example,  it  is  a  pathological  condition  when  the 
intercellular  substance  fails  to  be  impregnated  with  earthly  salts ; 
but  if  such  salts  are  deposited  in  the  somewhat  similar  fibrous  inter- 
cellular substance  of  the  closely  related  tissue  forming  a  ligament, 
the  process  is  then  morbid.  The  two  tissues  are  closely  related  in 
structure  and  are  built  up  by  cells  having  a  common,  not  very  remote, 
ancestry  :  yet  the  uses  the  cells  made  of  the  materials  brought  to 
them  are,  to  us,  very  different,  and,  as  yet,  inexplicable. 

Nor  do  we  know  much  concerning  the  way  in  which,  or  the 
extent  to  which,  normal  conditions  must  be  modified  in  order  to 
occasion  visible  morbid  changes  in  the  tissues.  We  do  know  that 
apparently  very  slight  alterations  in  those  conditions  may  cause  pro- 
found tissue-changes,  as  is  exemplified  in  the  cachexia  following 
extirpation  of  the  thyroid  gland  (see  p.  183).  The  amount  of 
thyroid  secretion  allotted  to  individual  cells  of  the  body  must  be 
almost  infinitesimal,  but  its  importance  is  strikingly  demonstrated 
when  the  cells  are  deprived  of  that  supply. 

In  this  case  we  have  at  least  an  inkling  of  how  slight  an  abnormal 
condition  may  suffice  to  work  profound  alterations  in  the  cellular 
economy.  When,  therefore,  we  meet  with  evidences  of  a  marked 
disturbance  of  the  processes  within  the  cells  of  a  tissue,  or  of  their 
formative  activities,  we  need  feel  no  surprise  if  an  explanation  of 
the  causes  underlying  those  morbid  manifestations  is  incomplete 
or  even  entirely  wanting. 

1.  Albuminoid  and  Fatty  Degenerations. — These  two  forms  of 
degeneration  are  frequently  associated  with  each  other,  and  have  so 
much  in  common  that  they  may  well  be  considered  together.  They 
both  affect  the  cells  of  the  parenchymatous  organs,  such  as  the 
kidney,  liver,  and  other  secreting  glands,  the  heart  and  other 
muscles. 

Albuminoid,  or  "  parenchymatous,"  degeneration  results  in  a 
swelling  of  the  cells,  with  an  increased  granulation  of  their  cytoplasm. 
The  granules  are  rendered  invisible  when  acted  upon  by  weak  acids 
or  alkalies,  and  are  considered  to  be  of  albuminoid  nature.  They 


DEGENERATIONS  AND  INFILTRATIONS. 


267 


are  formed  at  the  expense  of  the  cytoplasm,  or,  at  any  rate,  the 
cytoplasm  disappears  as  they  accumulate. 

If  the  change  be  only  moderate  in  degree,  it  is  possible  for  the 
cell  to  return  to  its  normal  condition.  The  granules  then  disap- 
pear, the  cell  recovers  its  original  size,  and  there  is  no  trace  of  the 
morbid  condition  left.  But  the  degeneration  may  be  too  extensive 
to  parmit  of  recovery.  The  cell  then  suifers  disintegration ;  the 
granules  become  more  abundant,  the  normal  cytoplasm  disappears, 

FIG.  245. 


*A  ^M&Z&tftmZggZ 


Parcnchymatous  nephritis,  a,  cross-section  of  a  convoluted  tubule  of  the  kidney,  the  lin- 
ing epithelium  of  which  is  the  seat  of  albuminoid  degeneration.  The  cells  are  swollen 
and  their  bodies  filled  with  abnormally  coarse  granules.  The  cells  to  the  left  are  so  far 
disintegrated  that  the  nuclei  have  lost  most  of  their  chromatin.  Such  cells  cannot 
recover.  The  cells  to  the  right  are  less  profoundly  altered  and  their  nuclei  retain  suf- 
ficient chromatin  to  stain  slightly.  These  cells  might,  perhaps,  recover.  Other  con- 
voluted tubules,  similarly  affected,  are  represented  in  oblique  section.  &,  tubule  with 
low,  unaffected  epithelium,  the  nuclei  of  which  stain  deeply ;  c,  round-cell  infiltration 
of  the  interstitial  tissue  in  the  neighborhood  of  a  Malpighian  body,  the  edge  of  which  is 
just  above  the  line  c.  Section  stained  with  haematoxylin  and  eosin. 

and  the  nucleus  falls  into  fragments  ("  karyolysis  "),  the  whole  cell 
being  reduced  to  a  granular  debris  exhibiting  no  evidence  of  organ- 
ization (Fig.  245). 


268  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

In  fatty  degeneration  the  process  is  similar  to  that  already 
described  as  taking  place  in  albuminoid  degeneration ;  but  here 
the  albuminoid  granules  are  replaced  by  globules  of  fat.  These 
vary  in  size  from  mere  granules  of  minute  dimensions  to  distinct 
globules  of  considerable  diameter  (Fig.  246).  The  fat  is  left 

FIG.  246. 


Fatty  degeneration  of  the  cardiac  muscle.  (Israel.)  In  some  portions  of  the  preparation  the 
cross-striations  of  the  contractile  substance  are  retained.  In  these  portions  the  fatty 
metamorphosis  has  not  taken  place.  In  other  places  the  contractile  substance  has  been 
destroyed  and  the  cells  are  charged  with  minute  granules  and  with  small  globules  of  fat. 
The  preparation  is  unstained,  so  that  the  nuclei  are  not  prominent.  They  have  been 
omitted  from  the  figure.  Specimen  prepared  by  teasing  the  fresh  tissue. 

unchanged  upon  treatment  with  weak  acids  or  alkalies,  and  is 
stained  a  dark  brown  or  black  by  solutions  of  osmic  acid  (see  Fig. 
186),  reactions  which  distinguish  fatty  from  albuminoid  granules. 
They  are,  furthermore,  dissolved  by  ether  or  strong  alcohol,  which 
leave  albuminoid  granules  undissolved.  In  specimens  which  have 
been  hardened  in  alcohol  the  fat  is  removed  from  the  cells,  which 
then  contain  little  clear  spaces  in  which  the  fat  was  situated  in  the 
fresh  condition  of  the  tissues.  This  removal  of  the  fat  is  likely 
to  be  still  more  perfect  if  the  specimen  has  been  embedded  in  cel- 
loidin,  solutions  of  which  contain  ether. 

Albuminoid  degeneration  occurs  in  acute  diseases,  such  as  the 
exanthemata,  typhoid  fever,  septicaemia,  etc.,  which  are  all  char- 
acterized by  fever.  It  also  occurs  in  cases  of  damage  to  the  tissues, 
insufficient  immediately  to  kill  the  cells,  but  great  enough  to  induce 
inflammation.  Because  of  this  frequent  association  with  inflam- 
matory changes  in  other  tissue-elements  albuminoid  degeneration 
has  been  termed  "acute  parenchymatous  inflammation."  The  dam- 
age may  be  the  result  of  some  externally  applied  injury,  or  it  may  be 
occasioned  by  a  sudden  diminution,  but  not  complete  arrest,  of  the 
nutrient  supply;  e.  g.,  by  the  incomplete  plugging  of  a  bloodvessel 
by  an  embolus.  Albuminoid  degeneration  may  also  be  the  result 


DEGENERATIONS  AND  INFILTRATIONS. 


269 


of  toxic  conditions  that  are  not  accompanied  by  rise  of  tempera- 
ture. 

In  all  the  foregoing  cases  the  cause  is  of  an  acute  nature,  acting 
rapidly  on  the  cells.  If  that  action  be  moderate  in  degree  and  per- 
sistent, the  albuminoid  degeneration  passes  into  fatty  degeneration. 
Hence  the  latter  has  been  called  "  chronic  pareuchymatous  inflam- 
mation." 

But  fatty  degeneration  is  not  always  preceded  by  albuminoid 
degeneration.  It  is  found  widely  distributed  in  the  cells  of  the 
body  in  anaemia  (Fig.  247),  leucaBmia,  and  phthisis,  and  in  many 

FIG.  247. 


Localized  fatty  degeneration  of  the  cardiac  muscle  in  a  case  of  pernicious  anaemia.  (Birch- 
Hirschfeld.)  The  three  or  four  fibres  at  the  bottom  of  the  figure  are  nearly,  if  not  quite, 
normal.  The  rest  of  the  fibres  are  the  seat  of  an  extensive  fatty  degeneration,  resulting 
in  a  complete  obliteration  of  the  normal  striations  of  the  contractile  substance.  Section 
of  the  fresh,  unstained  muscle.  The  nuclei,  being  unstained,  are  but  faintly  visible  in 
such  sections,  and  are  not  represented. 

toxic  conditions  that  are  of  a  subacute  or  chronic  character.  In  a 
more  localized  form  it  follows  those  diseases  of  the  bloodvessels 
which  interfere  with  a  normally  abundant  supply  of  blood  to  the 
parts  in  which  they  are  distributed.  It  appears,  again,  in  parts  the 
functional  activity  of  which  is  markedly  increased  without  a  corre- 
sponding increase  in  the  nutrient  supply.  For  example,  in  stenosis 
of  an  orifice  of  the  heart,  when  extra  work  is  thrown  on  the  cardiac 
muscle  and  the  nutrient  supply  is  insufficient  to  permit  of  hyper- 
trophy, the  muscle-cells  suffer  fatty  degeneration,  and  the  conse- 
quent weakening  of  its  walls  results  in  dilatation  of  that  particular 
cavity  which  is  subjected  to  the  difficult  task  of  urging  the  blood 
through  the  narrowed  orifice. 

If  we  examine  these  various  conditions  with  a  view  to  determin- 
ing their  effects  upon  the  cells,  we  shall  find  that  they  have  one 
common  feature.  There  is  in  all  of  them  a  lack  of  balance  between 
the  nutrient  supply  of  which  the  cells  can  avail  themselves  and 


270  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

the  consumption  of  material  made  necessary  by  the  work  required 
of  them. 

Under  these  circumstances  the  cells  appear,  first,  to  utilize  the 
food-materials  which  they  already  contain  as  an  accumulated  stock 
(metaplasm) ;  but  when  these  are  exhausted  they  are  forced  to  draw 
upon  those  materials  which  exist  as  a  part  of  their  own  organized 
structure,  if  they  are  to  maintain  their  functional  activities.  They 
thus  sacrifice  the  integrity  of  that  structure  in  order  to  do  the  work 
that  has  been  assigned  to  them  in  the  organization  of  the  whole  body. 

Now,  there  is  a  difference  in  the  immediate  availability  of  the 
various  classes  of  foods.  The  carbohydrates  appear  to  be  the  most 
susceptible  of  rapid  utilization ;  the  proteids  come  next,  and  the 
fats  last.  We  may  imagine,  then,  that  in  a  sudden  emergency  the 
cells  will  first  consume  the  greater  part  of  their  store  of  carbo- 
hydrates, then  the  proteids,  and  lastly  the  fats.  If  the  condition 
be  an  acute  one,  so  that  a  part  of  the  organized  proteids  are  utilized 
as  food,  this  utilization  is  not  complete,  but  the  proteids  are  split 
up  into  a  portion  that  can  be  most  readily  oxidized  and  turned  to 
account,  and  a  residual  portion,  which  appears  in  granular  form 
within  the  cytoplasm. 

We  may  also  imagine  that,  in  its  efforts  to  obtain  adequate 
nourishment,  the  cell  imbibes  an  excessive  amount  of  fluid  from 
its  surroundings. 

If  the  adverse  circumstances  are  extreme,  the  nucleus  is  also 
overworked  and  relatively  starved,  and  suffers  in  its  integrity 
(karyolysis).  When  the  nucleus  is  destroyed,  or  when  there  is  no 
longer  sufficient  cytoplasm  to  aid  it  in  its  assimilative  function,  a 
recovery  of  the  cell  becomes  impossible. 

Let  us  now  consider  how  this  conception  of  albuminoid  degen- 
eration may  serve  to  explain  its  occurrence  in  the  various  conditions 
in  which  it  is  found. 

In  fevers  the  rise  of  temperature  is  evidence  of  an  increased 
metabolism  within  the  body — i.  e.,  the  cells  of  the  body  are  more 
active  in  bringing  about  chemical  changes.  The  amount  of  urea 
eliminated  from  the  body  is  also  increased,  showing  that  those 
chemical  changes  involve  an  additional  consumption  of  proteids. 

In  febrile  conditions,  then,  the  cells  are  unusually  active  and  con- 
sume an  increased  amount  of  proteids.  Let  us  next  inquire  what  con- 
ditions exist  which  are  likely  to  interfere  with  their  nutrient  supply. 

The  source  of  all  nourishment,  which  is  not  gaseous,  being  the 


DEGENERATIONS  AND  INFILTRATIONS.  271 

food  taken  into  the  system,  it  is  evident  that  any  condition  inter- 
fering with  digestion  and  absorption  must  influence  the  general 
nutrient  supply.  In  fevers  the  glands  of  the  alimentary  tract,  as 
well  as  the  cells  of  other  organs,  are  affected  with  albuminoid 
degeneration.  Their  secretions  are  diminished  or  altered,  the  diges- 
tion arrested  in  greater  or  less  degree,  and  the  appetite  lost  or  per- 
verted. For  these  reasons  the  diet  must  be  adjusted,  not  only  to  the 
needs  of  the  patient,  but  also  to  his  powers  of  digestion.  But  this 
state  is  established  only  after  the  degenerative  changes  have  been 
inaugurated,  and  does  not  explain  the  way  in  which  they  start. 

If  we  bear  in  mind  that  the  febrile  condition  is  the  result  of  a 
toxic  state  of  the  blood  and  nutrient  fluids,  and  that  the  poisons 
present  are  probably  obnoxious  to  the  cells,  we  shail  find  no  dif- 
ficulty in  understanding  that  the  cells  might  reject  a  nutrient  supply 
so  vitiated.  Where  we  can  observe  the  action  of  cells,  we  know 
that  they  are  repelled  by  certain  substances,  and  it  appears  reason- 
able to  suppose  that  cells  which  we  cannot  directly  study  during 
life  possess  similar  powers  of  rejection.  If  this  view  be  correct, 
the  very  condition  which  induces  fever  would  also  interfere  with 
the  proper  nutrition  of  the  cells. 

The  causation  of  fever,  according  to  this  argument,  is  to  be 
sought  in  the  toxic  condition  of  the  blood  and  other  nutrient  fluids, 
the  poisons  disturbing  the  action  of  the  thermo-regulating  mechan- 
ism of  the  nervous  system  and  also  interfering  with  the  nutrition 
of  the  cells  of  the  body.  As  soon  as  fever  begins,  its  influence 
upon  the  cells  is  to  stimulate  their  activities,  for  we  know  that  a 
moderate  elevation  of  temperature  causes  an  increased  metabolism 
in  those  cells  that  we  can  study  while  alive.  It  is,  consequently,, 
not  necessary  that  a  direct  functional  demand  should  bear  upon 
the  cells  in  order  that  the  chemical  changes  within  them  be  aug- 
mented. The  rise  of  temperature  is  sufficient  to  account  for 
increased  metabolism,  which,  in  turn,  implies  a  liberation  of  heat, 
and,  therefore,  an  aggravation  of  the  morbid  condition.  The 
increase  of  noxious  waste-products  of  cellular  activity,  which  enter 
the  circulating  fluids,  may  also  add  to  its  toxicity. 

But,  in  addition  to  this  thermal  cause  of  increased  metabolism, 
the  toxaemia  throws  extra  work  upon  those  cells  that  are  charged 
with  the  function  of  maintaining  the  quality  of  the  blood  or  lymph. 
The  kidney  contains  such  cells,  and  is  one  of  the  organs  most  likely 
to  be  severely  affected  with  albuminoid  degeneration  (acute  paren- 


272  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

chymatous  nephritis,  Fig.  245).  The  spleen  and  lymphatic  glands 
are  also  exposed  to  an  increased  functional  demand,  and  respond  in 
an  increase  of  their  active  tissues,  which  may  pass  into  degener- 
ative conditions  if  the  task  be  greater  than  they  are  able  to  cope 
with  successfully. 

In  the  other  conditions  in  which  albuminoid  degeneration  is 
found  the  factors  determining  its  causation  appear  less  complicated 
than  in  the  fevers.  Many  of  the  acute  inflammatory  processes  are 
accompanied  by  a  rise  of  temperature,  due  to  the  absorption  of 
poisons  from  the  seat  of  the  inflammation,  and  then  the  degenera- 
tion will  be  more  widely  distributed  than  in  those  cases  in  which 
the  general  reaction  is  less  marked  or  entirely  absent.  But  the 
tissues  immediately  involved  in  the  inflammatory  process  will  suifer 
in  their  nutrition,  whether  toxaemia  be  present  or  not,  and  in  certain 
of  them  the  result  will  be  a  degeneration,  while  in  others  it  will  be 
necrosis  or  death.  In  the  case  of  albuminoid  degeneration  follow- 
ing incomplete  embolism  the  explanation  is  even  simpler;  for  here 
the  nutrition  is  directly  reduced  by  the  mechanical  effect  of  a  partial 
plugging  of  a  bloodvessel. 

In  all  the  cases  in  which  albuminoid  degeneration  occurs  in  a 
comparatively  pure  form  the  cause  is  an  acute  one — i.  e.,  the  cells 
are  called  upon  to  meet  a  sudden  change  of  condition  in  their 
activities  and  nutrition  :  the  former  being,  as  a  rule,  increased  ;  the 
latter,  probably  always  diminished. 

The  explanation  w^hich  can  be  offered  of  the  way  in  which  fatty 
degeneration  is  brought  about  is  very  similar  to  that  already  given 
for  albuminoid  degeneration. 

In  fatty  degeneration  the  emergency  which  the  cells  have  to  meet 
is  less  sudden  than  in  albuminoid  degeneration.  The  adverse  con- 
ditions to  which  they  are  subjected  are  more  slowly  developed, 
though  not  necessarily  less  serious.  The  cells  appear  to  be  able  to 
accommodate  themselves  to  a  considerable  extent  to  the  abnormal 
circumstances,  but  eventually  their  powers  of  metabolism  are  dis- 
turbed and  they  are  incapable  of  utilizing  the  less  readily  available 
food-materials.  When  the  organized  proteids  are  then  drawn  upon 
their  nitrogen  appears  to  be  completely  used,  so  that  no  residual 
albuminoid  substances  are  deposited  in  granular  form,  but  a  rem- 
nant of  the  cytoplasm,  free  from  nitrogen  and  taking  the  form  of 
fat,  the  least  readily  oxidized  form  of  food,  is  left.  If,  now,  the 
oells  continue  to  appropriate  and  utilize  albuminoid  food-material, 


DEGENERATIONS  AND  INFILTRATIONS.  273 

this  fatty  residue  would  accumulate  within  the  cytoplasm.  Fatty 
foods  would,  of  course,  be  little,  if  at  all,  utilized. 

This  leads  to  the  inference  that  one  of  the  chief  features  in  the 
disturbed  metabolism  of  the  cell  is  an  inability  to  bring  about  the 
complete  oxidations  that  normally  take  place  in  the  cytoplasm,  and 
when  we  examine  the  conditions  in  which  fatty  degeneration  occurs 
we  notice  that  a  group  of  them  are  such  as  would  involve  a  dimin- 
ished amount  of  oxygen  in  the  blood.  This  is  manifest  in  cases  of 
anaemia,  advanced  phthisis,  and  poisoning  with  carbonic  oxide,  which 
destroys  the  respiratory  value  of  the  haemoglobin. 

In  the  subacute  and  chronic  toxic  conditions — e.  (/.,  such  cases  of 
poisoning  by  phosphorus  or  arsenic  in  which  the  patient  survives 
for  a  considerable  time — the  blood  probably  contains  a  sufficiently 
abundant  supply  of  oxygen  for  the  needs  of  the  tissues.  But  intra- 
cellular  respiration  is  a  complicated  process  ;  not  a  simple  and  direct 
burning  of  substances  occasioned  by  their  immediate  conversion  into 
fully  oxidized  compounds  when  brought  into  relations  with  free 
oxygen.  The  food-materials  are  split  up  within  the  cell  into  com- 
pounds of  simpler  constitution,  some  of  which  receive  a  sufficient 
amount  of  oxygen,  from  the  original  material  of  which  they  are 
derivatives,  to  satisfy  their  affinities,  and  are,  therefore,  stable ; 
while  others  are  organic  substances  in  a  chemically  reduced  state, 
which  unite  with  the  free  oxygen  that  may  be  accessible.  The  oxi- 
dation is  not  caused  by  the  presence  of  free  oxygen,  but  is  an  inci- 
dent in  the  chemical  changes  carried  on  by  the  cell. 

In  the  toxic  conditions  leading  to  fatty  degeneration  this  intra- 
cellular  oxidation  is  probably  interfered  with  through  the  action  of 
the  poisons  upon  the  cytoplasm,  and,  as  a  result,  the  least  easily 
oxidizable  substance,  fat,  remains  as  an  unutilized  residue.  The 
poisons  at  the  same  time  probably  interfere  with  the  nutrition  of  the 
cell,  which  draws  upon  its  organized  proteids  for  a  supply  of  nitro- 
gen, leaving  again  a  remnant  of  unavailable  fat. 

It  is  easily  comprehensible  that  relative  overwork  may  have  the 
same  effect  upon  the  cell  as  relative  innutrition.  The  fatty  degen- 
eration of  the  heart-muscle  as  the  result  of  stenosis  or  of  valvular 
insufficiency  at  one  of  its  orifices  would,  therefore,  be  explained  as 
an  example  of  a  lack  of  balance  between  the  supply  and  consump- 
tion of  food  in  the  economy  of  the  cardiac  cells.  Relative  overwork 
of  the  heart  is  also  one  of  the  effects  of  marked  anaemia.  The 
anaemic  condition  involves  a  diminished  supply  of  oxygen,  from 

18 


274  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

which  the  heart,  as  well  as  the  other  tissues,  suffers.  But  the 
demand  for  oxygen  on  the  part  of  the  general  economy  requires  an 
acceleration  of  the  circulation ;  this  throws  extra  work  upon  a 
relatively  starved  heart. 

It  is  evident,  from  the  foregoing  considerations,  that  albuminoid 
and  fatty  degenerations  must  be  very  common  conditions  in  the  cells 
of  the  body.  Their  close  etiological  similarity  makes  it  obvious, 
also,  that  they  must  very  frequently  be  associated  with  each  other, 
either  in  the  same  cell  or  in  different  cells  of  the  same  organ.  The 
fact  that  fatty  degeneration  is  often  a  sequel  of  albuminoid  degen- 
eration may  be  explained  as  the  result  of  a  toxic  or  other  condition, 
which  has  been  sudden  in  its  onset,  but  has  declined  in  intensity 
with  the  lapse  of  time.  Or  it  may  be  possible  that  the  cells  are 
able  gradually  to  adapt  themselves,  in  a  measure,  to  the  new  con- 
ditions under  which  they  must  do  their  work,  and  that  they  become 
able  to  utilize  more  completely  the  foods  they  receive ;  leaving  a 
fatty,  instead  of  an  albuminoid,  residue. 

Fatty  degeneration,  like  albuminoid  degeneration,  may  lead  to  a 
total  destruction  of  the  cell,  leaving  the  fatty  globules  free,  or 
recovery  may  take  place  on  the  subsidence  of  the  cause. 

2.  Cheesy  degeneration  is  a  term  applied   to  an  association   of 
albuminoid  and  fatty  degenerations  with   necrosis,  in  which    the 
detritus  of  the  tissues  forms  a  dry  material,  somewhat  resembling 
the  softer  varieties  of  cheese.     Under  the  microscope  this  cheesy 
material  has  a  finely  granular  appearance,  with  here  and  there  small 
fragments  of  nuclear  chromoplasm  which  still  retain  their  affinity  for 
nuclear  dyes. 

3.  Fatty  Infiltration. — Essentially  different  from  fatty  degenera- 
tion is  an  accumulation  of  fat  in  cells  as  the  result  of  their  over- 
feeding.    It  may  be  due  to  an  excessive  reception  of  fat  by  the 
cells,  but  this  is  not  necessarily  the  case.     A  supply  of  any  form 
of  food  that  is  in  considerable  excess  of  the  needs  of  the  body  may 
result  in  a  fatty  infiltration  of  its  cells,  for  fat  is  the  least  readily 
consumed  variety  of  food,  and  where   the  other  varieties  are  in 
great  abundance  it  may  be  guarded  against  destruction  and  remain 
in  the  tissues.     Furthermore,  a  part  of  the  excess  of  other  food- 
materials  may  be  converted  into  fat  within  the  cells  and  be  retained 
by  them. 

Fatty  infiltration  is  a  normal  condition  of  many  cells.  Those 
which  form  the  characteristic  element  in  adipose  tissue  (Fig.  65)  are 


DEGENERATIONS  AND  INFILTRATIONS.  275 

connective-tissue  cells  that  have  undergone  extensive  fatty  infiltra- 
tion. A  transitory  fatty  infiltration  is  also  normal  in  the  cells  of 
the  liver  (Fig.  248). 

FIG.  248. 


Cells  from  the  human  liver,  normal.  (Orth.)  a,  cells  free  from  fat.  The  isolated  cell  to  the 
right  contains  two  nuclei  and  three  or  four  granules  of  pigment.  The  three  lower  cells, 
6,  are  infiltrated  with  globules  of  fat.  It  will  be  noticed  that  those  three  cells  contain  as 
much  cytoplasm  as  the  two  contiguous  cells,  a.  This  is  taken  as  an  indication  that  the 
fat  is  superadded  to  the  cytoplasm,  and  has  not  been  produced  at  the  expense  of  part  of 
the  organized  substance  of  the  cell.  This  does  not  imply  that  the  fat  was  necessarily 
taken  into  the  cell  as  such,  for  it  may  have  been  produced  within  the  cell  from  food-mate- 
rials ;  but  it  has  not  been  produced  at  a  sacrifice  of  the  organized  materials  forming  an 
essential  part  of  the  living  cell. 

The  globules  of  fat  form  a  part  of  the  metaplasm  of  the  cells  in 
which  they  are  situated ;  i.  e.,  they  do  not  constitute  an  integral 
part  of  the  cytoplasm,  but  lie  within  it,  leaving  it  intact,  unless  the 
accumulation  is  so  great  that  the  functions  of  the  cell  are  interfered 
with.  Then  the  cytoplasm  may  suffer  atrophy  and  its  usefulness  be 
diminished. 

It  is  not  possible  to  lay  down  any  practical  rule  for  distinguishing 
between  fatty  infiltration  and  fatty  degeneration  when  cells  are 
examined  under  the  microscope,  beyond  the  general  statement  that 
in  degeneration  there  is  a  corresponding  destruction  of  the  cyto- 
plasm as  the  fat  accumulates.  In  fatty  infiltration  the  globules  of 
fat  are  rather  more  apt  to  coalesce  with  each  other  than  in  fatty 
degeneration,  so  that  the  globules  appear  larger.  This  is  not  in- 
variably the  case,  however,  the  behavior  of  the  fat  in  this  respect 
differing  in  different  kinds  of  cell. 

4.  Glycogenic  Infiltration. — This  is  a  condition  analogous  to  fatty 
infiltration,  but  the  stored  excess  of  food-material  in  this  case  be- 
longs to  the  class  of  carbohydrates.  The  condition  is  found  in  the 
cells  of  the  convoluted  renal  tubules  in  cases  of  diabetes  mellitus, 
sometimes  in  the  leucocytes  in  inflammatory  foci,  and  occasionally 
in  the  cells  of  tumors  where  the  functional  activities  of  the  cells 
are  in  abeyance  and  only  their  formative  powers  call  for  a  consump- 
tion of  food. 


276  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

The  glycogen  occurs  either  in  granules  or  in  small,  irregular 
masses  within  the  cytoplasm  (Fig.  249).  It  is  soluble  in  water,  and 
its  detection  is  a  matter  of  difficulty  unless  special  methods  of  prep- 


FIG.  249. 

9 


'^fi-A,    *vvs!«r* 


a, 


Glycogenic  infiltration  of  the  cells  in  an  endothelioma.  (Driessen.)  a,  cell  crowded  with 
granular  masses  of  glycogen  ;  6,  fibrous  tissue  forming  the  stroma  of  the  tumor  ;  c,  space 
within  the  growth  containing  blood.  Section  from  an  endothelioma  of  bone,  stained 
with  a  solution  of  iodine  and  gum-arabic  in  water.  Iodine  stains  glycogen  brown.  The 
nuclei  and  cytoplasm  of  the  cells  are  not  represented.  A  section  from  the  same  tumor 
after  the  extraction  of  the  glycogen  and  staining  with  nuclear  dyes  is  shown  in  Fig.  222. 

aration  are  employed  to  retain  it  in  situ  and  so  facilitate  its  recog- 
nition. When  it  is  dissolved  from  the  cytoplasm  it  leaves  small, 
clear,  empty  spaces  behind. 

Glycogenic  infiltration  is  a  normal  condition  in  the  cells  of  the 
liver  and  in  muscular  fibres.  In  the  latter  situation  it  serves  as  a 
store  of  rapidly  available  energy,  which  can  be  drawn  upon  during 
the  functional  activity  of  the  cells.  In  the  liver  it  serves  a  similar 
purpose  for  the  whole  body. 

5.  Serous  Infiltration. — In  oedematous  conditions  of  the  tissues 
their  cells  sometimes  imbibe  fluid  from  their  surroundings,  which 
appears  as  clear  drops  or  vacuoles  within  the  cytoplasm  (Fig.  250). 
The  condition  may  subsequently  subside,  or  it  may  lead  to  a  disin- 
tegration of  the  cytoplasm  and  nucleus.  The  cell  then  undergoes 
a  form  of  destruction  very  closely  resembling  that  in  albuminoid 


DEGENERATIONS  AND  INFILTRATIONS. 


277 


degeneration.  Serous  infiltration,  more  or  less  complicated  with 
albuminoid  degeneration,  also  occurs  in  inflammations  when  the 
serous  constituent  of  the  exudate  is  prominent. 

6.  Mucous  Degeneration. — This  form  of  degeneration  has  its  nor- 
mal analogue  in  the  elaboration  of  mucus  by  the  epithelial  cells 
covering  many  of  the  mucous  membranes  or  lining  mucous  glands. 

FIG.  250. 


Vaciiolation  of  striated  muscle.  (Volkmann.)  The  specimen  is  from  the  rectus  abdominis 
muscle  from  a  case  of  typhoid  fever.  The  cross-sections  of  the  muscle-fibres  contain  spaces 
within  the  contractile  substance,  which  are  filled  with  a  clear,  fluid  serum.  The  fibres 
so  infiltrated  are  larger  than  those  containing  no  such  vacuoles.  The  cavities  are,  therefore, 
not  produced  at  the  expense  of  the  contractile  substance.  Between  the  fibres  is  the  in- 
termuscular,  vascularized  fibrous  tissue,  forming  the  interstitial  tissue  of  the  muscu- 
lar organ. 

But  the  elaboration  of  mucin  is  not  confined  to  epithelium.  It  may 
be  produced  by  the  cells  of  the  connective  tissues,  appearing  among 
the  intercellular  substances.  This  is  most  marked  in  mucous  tissue, 
where  the  general  character  of  the  tissue  is  determined  by  the 
mucus  in  the  intercellular  substance.  There  is  also  a  comparatively 
small  amount  of  mucus  in  other  forms  of  connective  tissue,  espe- 
cially in  the  fibrous  varieties. 

Under  morbid  conditions,  which  \ve  are  not  able  exactly  to  define, 
this  production  of  mucus  is  increased.    In  epithelial  and  other  cells 


278  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

its  production  may  involve  a  destruction  of  the  cytoplasm,  which 
appears  to  be  sacrificed.  A  similar  transformation  or  replacement 
of  the  normal  intercellular  substances  may  also  occur  in  the  connec- 
tive tissues,  such  as  bone,  cartilage,  fat,  or  fibrous  tissue,  which  then 
contain  more  than  the  normal  proportion  of  mucin.  This  propor- 
tion may  be  so  great  as  to  alter  the  physical  properties  of  the  tissue. 
In  these  cases  the  cells  may  undergo  mucous  degeneration,  or  they 
may  ultimately  suffer  a  fatty  degeneration.  It  is  a  question  to  what 
extent  the  cells  are  active  in  the  substitution  of  mucous  for  the  usual 
intercellular  substances,  the  manner  in  which  it  is  produced  being 
as  yet  undetermined. 

The  mucus  is  a  clear,  viscid  fluid,  which  appears  to  be  a  mixture 
of  various  substances  containing  either  mucin  or  pseudomucin. 
These  substances  are  precipitated  by  alcohol,  so  that  in  hardened 
specimens  the  mucus  becomes  granular  or  is  streaked  with  linear 
coagula.  Hsematoxylin  usually  stains  the  whole  mass  a  faint  blue ; 
the  granules  and  streaks  a  little  more  intensely  than  the  clearer  por- 
tions. This  staining  serves  to  distinguish  the  mucus  from  a  serous 
fluid,  which  is  also  made  granular  by  the  coagulating  influence  of 
alcohol  upon  the  albumin  it  contains. 

Mucous  degeneration  of  the  epithelia  is  a  frequent  accompani- 
ment of  inflammation  of  the  mucous  membranes,  where  it  appears  to 
be  due  to  an  excessive  stimulation  of  the  functional  activities  of  the 
cells.  A  similar  mucous  degeneration  of  epithelial  cells  is  also  very 
common  in  tumors ;  e.  g.,  the  cystomata  of  the  ovary  and  colloid 
cancer. 

7.  Colloid  Degeneration. — This  is  a  form  of  degeneration  in  which 
the  substance  of  cells  is  converted  into  a  clear,  homogeneous,  gelat- 
inous material  of  greater  consistency  than  mucus,  and,  unlike  the 
latter,  is  not  precipitated  by  alcohol,  so  that  in  hardened  specimens 
it  retains  its  homogeneous  appearance. 

The  production  of  colloid  seems  to  be  normal  in  the  thyroid 
gland  after  the  attainment  of  a  certain  age.  In  this  situation  the 
colloid  material  is  formed  in  the  cells  of  the  alveoli  and  then  dis- 
charged into  their  lumina,  Avhere  it  forms  a  mass  that  may  com- 
pletely fill  its  cavity  (Fig.  154) ;  but  the  cells  of  the  thyroid  not 
infrequently  suffer  destruction  in  the  elaboration  of  the  colloid 
material,  so  that  even  here  the  process  partakes  of  a  degenerative 
character. 

The   material    forming   the  hyaline   casts   in   various  kinds   of 


DEGENERATIONS  AND  INFILTRATIONS.  279 

nephritis  appears  to  be  colloid  elaborated  by  the  cells  lining  the 
renal  tubules,  but  those  casts  may  not  always  owe  their  origin  to  this 
form  of  degeneration. 


FIG.  251. 


FIG.  252. 


•.  f. 


Hyaline  degeneration.    (Ernst.) 

Fig.  251. — Hyaline  degeneration  of  cells  in  the  choroid  plexus.  In  this  case  the  hyaline 
material  appears  to  be  derived  from  the  cytoplasm  of  the  cells,  thepi'ocess  constituting 
a  true  degeneration.  Transitional  conditions  from  the  unchanged  cells  to  masses  of 
hyaline  without  traces  of  cellular  structure  are  found  in  the  specimen. 

Fig.  252.— Hyaline  degeneration  of  the  capillary  walls  in  a  psammoma  of  the  dura  mater. 
Here  the  endothelial  lining  of  the  capillaries  is  intact,  the  hyaline  material  being  out- 
side of  it.  This  disposition  of  the  hyaline  would  lead  to  the  inference  that  in  this  case 
it  was  the  result  of  infiltration. 

It  is  probable  that  the  composition  of  colloid  is  not  always  the 
same.  It  is  identified  by  the  facts  that  it  is  a  clear,  structureless 
substance,  derived  from  cells  and  not  presenting  the  characteristics 
of  mucus.  The  causes  and  mode  of  its  production  are  unknown. 


280  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

8.  Hyaline    Degeneration. — This  term  is  used    to    designate  the 
occurrence  of  a  material  similar  to  colloid,  which  appears  chiefly  in 
the  intercellular  substances  or  in  the  interstices  of  the  tissues,  and  is 
apparently  not  immediately  derived  from  the  substance  of  cells.     It 
is  a  question  whether  it  should,  in  such  cases,  be  regarded  as  a 
degeneration — i.  e.9  the  result  of  a  transformation  of  pre-existent 
normal  structures — or  whether  it  is  not  a  form  of  infiltration,  the 
material  being  simply   deposited  between   the   normal   structures, 
which  may  atrophy  and  disappear  in  consequence  of  its  presence. 
Its  most  common  site  is  beneath   the  endothelial  linings  of   the 
bloodvessels,  where  it  forms  a  homogeneous  layer,  greatly  thicken- 
ing the  vascular  wall  and  often  causing  a  narrowing  of  the  lumen 
of  the  vessel  (Figs.  251   and   252).     It  may  also  affect  the   fibrous 
tissues,  replacing  the  intercellular  substances  with  hyaline  material, 
made  up  of  an  agglomeration  of  little  masses,  or  appearing  quite 
homogeneous.     The  cells  of  the  tissues  gradually  undergo  atrophy 
and  disappear,  but  do  not  seem  in  most  cases  to  suffer  a  transforma- 
tion into  hyaline  substance.     In  some  instances,  however,  the  cyto- 
plasm of  the  cells  appears  to  undergo  a   hyaline   transformation 
(Fig.  251). 

A  hyaline  transformation  sometimes  affects  thrombi,  which  lose 
their  fibrinous  character  and  become  homogeneous. 

Hyaline  material  may  take  a  faint  bluish  tint  when  treated  with 
hsematoxylin,  or  it  may  remain  colorless. 

Various  attempts  have  been  made  to  define  more  clearly  the  con- 
ceptions of  colloid  and  hyaline  substances,  and  to  distinguish  them 
by  means  of  reactions  with  different  staining-fluids.  These  attempts 
have  not  led  to  satisfactory  results,  probably  because  the  colloid 
and  hyaline  substances  are  mixtures  of  various  chemical  compounds  ; 
the  whole  subject  awaits  further  investigation. 

9.  Keratoid  Degeneration. — This  form  of  degeneration  is  a  trans- 
formation of  the  cytoplasm  into  a  substance  called  keratin,  which 
gives  to  horn,  the  nails,  etc.,  their  peculiar  character.     It  is  nor- 
mally produced  in  the  epidermis,  where  this  degenerative  process  is 
not  pathological.     The  transformation  appears  to  involve  the  pre- 
liminary formation  of  a   substance  called  eleidin  (Fig.   175),   the 
chemical  nature  of  which  is  unknown,  which  subsequently  changes 
into  keratin.     These  two  substances  may  be  distinguished  by  the 
facts  that  eleidin  is  deeply  stained  by  carmine  and  not  by  fuchsin, 
while  keratin  is  readily  stained  by  the  latter  dye. 


DEGENERATIONS  AND  INFILTRATIONS. 


281 


The  cells  in  the  epithelial  pearls  of  epitheliomata  often  undergo 
these  degenerative  changes,  producing  large  masses  of  eleidin  or 
keratin.  The  change  in  these  cases  may  be  considered  as  due  to 
a  retention  of  this  normal  tendency  by  the  epidermal  epithelium 
under  the  abnormal  conditions  in  which  it  is  placed  in  the  tumor. 
In  those  cases  of  metaplasia  in  which  columnar  epithelium  becomes 
converted  into  the  stratified  variety  the  susceptibility  to  keratoid 
degeneration  is  an  acquired  character,  columnar  epithelium  under 
normal  conditions  never  suffering  this  change. 

10.  Amyloid  Infiltration. — The  change  in  the  tissues  known  by 
this  name,  or  that  of  amyloid  degeneration,  has  many  resemblances 
to  hyaline  degeneration  (or  infiltration).  Amyloid  differs,  however, 
from  the  hyaline  substances  in  being  recognizable  by  means  of  a 
number  of  characteristic  reactions,  although  they  vary  considerably 

FIG.  253. 


Amyloid  infiltration  in  the  liver.  (Thoma.)  a,  lumen  of  an  intralobular  capillary,  sur- 
rounded by  the  endothelial  wall  of  the  vessel ;  6,  amyloid  substance  immediately 
beneath  the  endothelium ;  c,  epithelial  cells  of  the  hepatic  parenchyma,  some  of  which 
show  a  fatty  infiltration. 

in  sharpness  in  different  cases,  and  give  rise  to  the  suspicion  that 
the  amyloid  substance  is  not  always  of  constant  chemical  composi- 
tion, or  that  it  may  be  transformed  into  other  substances  of  similar 
physical  and  optical  properties. 

Amyloid  is  a  nitrogenous  material,  which  is  stained  a  dark  brown 


282  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

by  aqueous  solutions  of  iodine,  while  the  normal  tissues  acquire  a 
yellow  color.  Under  the  microscope  the  brown  color  has  a  marked 
reddish  tinge.  Solutions  of  methyl-violet  give  amyloid  a  red  color 
and  stain  the  rest  of  the  tissues  blue  or  bluish-violet.  It  is  upon 
these  reactions,  and  not  upon  the  optical  appearance  of  the  material 
when  unstained,  that  the  recognition  of  amyloid  depends. 

Its  most  frequent  situation  is  in  the  walls  of  the  smaller  blood- 
vessels, where  it  lies  in  the  deeper  layers  of  the  intima  or  in  the 
muscular  coat.  It  may  also  be  deposited  around  the  endothelial 
walls  of  the  capillaries  (Fig.  253). 

Amyloid  infiltration  occurs  in  syphilis,  advanced  tuberculosis 
(especially  of  bone),  long-continued  suppuration,  and  similar  condi- 
tions in  which  there  is  profound  cachexia.  It  evidently  depends 
upon  conditions  of  marked  malnutrition  or  chronic  toxic  conditions, 
and  it  is  believed  that  its  occurrence  depends  upon  the  inability  of 
the  tissue-cells  to  utilize  the  proteids  that  are  present  in  the  inter- 
stitial serum.  These  are  thought  to  accumulate  and  gradually  be- 
come transformed  into  amyloid.  The  deposition  of  amyloid,  accord- 
ing to  this  hypothesis,  would  depend  primarily  upon  a  lack  of  power 
to  assimilate  proteids  on  the  part  of  the  cells. 

The  presence  of  amyloid  between  the  cellular  elements  of  the 
tissue  interferes  with  their  nutrition,  and  they  suifer  atrophy. 

11.  Calcareous  Infiltration  (Figs.  254  and  255). — There  appears  to 
be  a  marked  affinity  between  necrosed  tissues,  or  tissues  of  low  vital- 
ity, and  the  salts  of  lime  that  are  found  in  the  circulating  fluids  of 
the  body,  which  leads  to  a  deposit  of  the  latter  within  those  tis- 
sues. The  cheesy  material  that  results  from  tubercular  or  other  proc- 
esses is  prone  to  this  form  of  infiltration.  Cicatricial  tissue,  when 
abundant  and  poorly  nourished,  may  also  be  the  seat  of  lime-deposits. 
Similar  deposits  are  sometimes  associated  with  those  of  urates  in  the 
inflammatory  nodules  of  low  vitality  that  characterize  gout.  Bits 
of  organic  or  other  foreign  matter  that  are  exposed  to  fluids  contain- 
ing salts  of  lime  are  liable  to  become  encrusted  with  a  coating  of  cal- 
careous material.  This  is  the  origin  of  many  renal  and  other  calculi 
and  of  the  vein-stones  that  form  around  small  thrombi  of  occasional 
occurrence  where  the  circulation  is  very  sluggish ;  e.  g.,  in  the 
venous  plexuses  within  the  pelvis,  or  behind  the  valves  that  occur 
in  the  course  of  most  of  the  veins.  Calcification  of  cartilage  is  also 
common  after  the  individual  has  attained  a  certain  age.  Tumors 
in  which  the  tissues  are  of  low  vitality  or  have  degenerated  are 


DEGENERATIONS  AND  INFILTRATIONS. 


283 


also  liable  to  calcareous  infiltration.  That  infiltration  appears, 
then,  to  be  always  secondary  to  some  morbid  process  lowering  the 
vitality  of  the  tissues. 

Calcareous  infiltration  may  serve  as  a  type  of  infiltrations  with 
other  materials,  such  as  urates,  and  of  the  formation  of  concretions ; 
for  example,  gall-stones.  These  and 
other  concretions  contain  a  nucleus  of 
organic  or  other  nature,  upon  which 
the  salts  are  deposited  from  their  solu- 
tions very  much  as  sugar  crystallizes 
upon  threads  suspended  in  a  syrup. 

12.  Degeneration  of  Nerves. — If  a 
nerve-fibre  be  severed  from  its  connec- 
tion with  the  ganglion-cell  of  which  it 
is  a  process,  it  suffers  disintegration. 
The  medullary  sheath  breaks  up  into 
a  number  of  globular  masses,  which 
are  subdivided  and  eventually  ab- 
sorbed. The  axis-cylinder  becomes 
swollen,  granular,  and  also  disappears. 
If  the  ganglion-cell  retains  its  vitality. 

FIG.  254. 


Fig.  254.— Calcareous  infiltration  of  renal  glomeruli,  secondary  to  hyaline  degeneration  of 
the  capillary  walls,  obliteration  of  the  vascular  lumen,  and  death  of  the  tissue.  The 
glomerulus  to  the  left  shows  a  slight  granular  deposit  of  calcareous  material  in  the 
hyaline  glomerulus.  The  figure  to  the  right  shows  the  organic  base  almost  completely 
obscured  by  calcareous  granules.  (Ribbert.) 

Fig.  255.— Calcareous  infiltration  of  the  cardiac  muscle.  (Langerhans.)  a,  degenerated  car- 
diac muscle ;  b,  muscular  fibres  impregnated  with  lime-salts.  The  specimen  was  taken 
from  a  case  of  chronic  lead-poisoning.  The  cells  which  are  the  seat  of  the  calcareous 
infiltration  must  have  been  dead  for  a  considerable  time  before  the  death  of  the  indi- 
vidual. 

it  may  regenerate  the  nerve  by  the  development  of  a  new  process. 
If,  however,  the  ganglion-cell  has  been  destroyed,  regeneration  does 
not  take  place.  This  exemplifies  the  statement,  made  in  the  chapter 
on  the  cell,  that  portions  of  cells  which  were  devoid  of  a  nucleus 
could  not  continue  their  existence. 


CHAPTER  XXI. 

ATROPHY. 

ATROPHY  is  a  diminution  in  the  size  of  a  part,  due  to  a  deficient 
nutrition  of  its  constituents,  which  is  neither  so  rapid  nor  so  destruc- 
tive as  to  cause  necrotic,  degenerative,  or  inflammatory  changes. 
The  tissue-elements  appear  comparatively  normal  under  the  micro- 
scope, but  are  either  all  or  in  part  diminished  in  size.  This  dimi- 
nution in  size  is  frequently  accompanied  by  an  increased  depth  of  the 
usual  coloring  of  the  tissue-elements,  or  with  th'e  appearance  of 
granules  of  pigment  (Fig.  256). 

FIG.  256. 


Brown  or  senile  atrophy  of  the  heart.    (Ribbert.)    The  muscle-fibres  are  reduced  in  diameter. 
At  the  ends  of  the  nuclei  are  collections  of  pigment-granules. 

The  cause  of  atrophy  may  operate  almost  directly  upon  the  cells 
involved,  or  it  may  indirectly  influence  the  nutrition  of  the  cells 
through  lesions  in  the  circulatory  or  nervous  system,  or  through  an 
interference  with  the  processes  of  general  nutrition  maintaining  the 
whole  body. 

1.  Functional  Atrophy. — It  appears  to  be  a  general  principle  gov- 
erning living  organisms  that  functional  activity,  within  a  certain 
normal  range,  is  necessary  to  the  maintenance  of  the  normal  nutri- 
tion of  a  part.  When  the  required  degree  of  functional  activity 
is  not  called  forth,  the  nutrition  of  the  part  suffers  and  it  undergoes 
atrophy.  Paralyzed  muscles  lose  their  normal  size  through  innutri- 
tion following  their  disuse.  Secreting  glands  may  also  suffer  atrophy 

284 


ATROPHY. 


285 


when  there  is  no  longer  an  adequate  call  for  their  functional  activ- 
ities. 

This  form  of  atrophy  is  probably  attributable  in  some  measure 
to  a  diminished  flow  of  blood  to  the  part,  for  in  health,  when  the 
functional  activity  of  an  organ  is  called  into  play,  there  is  an  in- 
creased volume  of  blood  conveyed  to  that  organ.  But  this  element 
in  the  innutrition  does  not  account  for  the  whole  process.  The 
intracellular  metabolism  also  falls  below  the  normal  level,  and  this 
appears  to  reduce  the  state  of  nutrition  of  the  cellular  constituents. 

2.  Pressure-atrophy  (Figs.  257  and  258). — When  a  part  is  sub- 
jected to  moderate  but  constant,  or  oft-repeated  pressure,  it  under- 
goes atrophy  through  a  disturbance  in  its  nutrition.  This  may  be 

FIG.  257. 


Section  from  an  emphysematous  lung.  (Ribbert.)  The  pulmonary  alveoli  are  enlarged ;  their 
walls  are  stretched  and  thinned ;  atrophied  because  of  repeated  excessive  air-pressure 
within  the  alveoli.  In  more  extreme  cases  of  emphysema  the  atrophy  of  the  alveolar 
walls  may  lead  to  their  total  destruction  in  places,  so  that  the  cavities  of  neighboring 
alveoli  communicate.  (Compare  with  Fig.  150.) 

partly  due  to  a  direct  influence  exerted  by  the  pressure  upon  the 
processes  carried  on  in  the  cells  of  the  tissue,  but  it  is  probable  that 
interference  with  the  circulation,  including  the  lymph-currents,  has 
a  greater  influence  in  bringing  about  the  lack  of  nourishment.  Ex- 
amples of  this  form  of  atrophy  are  furnished  by  cases  in  which  a 
contracting  cicatricial  tissue  is  formed  between  the  parenchymatous 
cells  of  an  organ,  as  the  result  of  a  chronic  interstitial  inflammation. 
Those  cells  then  undergo  atrophy  and  may  eventually  disappear  (Fig. 


286  HISTOLOGY  OF  THE  MORBID   PROCESSES, 

288).  In  passive  hypersemia  of  the  liver  the  cells  situated  around  the 
central  veins  of  the  lobules  suffer  atrophy.  This  is  due  in  part  to 
the  pressure  exerted  upon  them,  in  part  to  an  interruption  of  the 
lymphatic  circulation,  and  in  part  to  the  fact  that  the  blood  reaches 
them  last  in  its  course  through  the  organ  and  is  probably  less  richly 
provided  with  oxygen  and  other  nutritive  materials  than  when  it 

FIG.  258. 


Lobule  of  the  liver,  showing  atrophy  from  chronic  passive  congestion.  (Kibbert.)  In  the 
centre  is  the  central  vein,  with  slightly  thickened  walls.  Surrounding  this  are  the  di- 
lated capillaries,  forming  the  intralobular  vessels,  between  which  are  the  atrophic  liver- 
cells  containing  pigment.  This  pigment  is  probably  of  biliary  origin.  The  pressure 
upon  the  cells  must  interfere  with  the  discharge  of  the  bile  through  the  bile-capillaries 
(Figs.  127  and  128),  and  lead  to  an  accumulation  of  its  constituents  within  the  cells, 
where  the  pigment  collects. 

passed  through  the  other  parts  of  the  vascular  system  within  the 
liver.  The  capillaries  are  enlarged  around  the  central  vein  ;  the 
hepatic  cells  between  them  are  diminished  in  size  and  pigmented 
(Fig.  258). 

The  growth  of  tumors  may  exert  a  pressure  upon  neighboring 
parts,  causing  their  atrophy,  the  explanation  of  which  is  similar  to 
that  of  atrophy  of  the  liver  as  the  result  of  passive  hypersemia. 
Pressure  upon  a  tissue  does  not  always,  however,  occasion  atrophy. 
If  the  function  of  a  part  be  to  resist  pressure,  an  increase  of  press- 
ure may  lead  to  hypertrophy,  provided  the  nutrient  supply  be 
sufficient.  Thus  pressure  upon  the  walls  of  a  bloodvessel  may 
cause  them  to  increase  in  thickness. 

Aside  from  the  two  forms  already  mentioned,  atrophy  may  be  the 
result  of  a  diminution  in  the  nutritive  supply :  local,  as  the  result 
of  disease  in  the  vessels  of  a  part ;  general,  when  all  the  vessels  are 


ATROPHY.  287 

affected  with  disease,  or  when  the  general  nutrition  of  the  body  is 
reduced.  Both  these  causes  operate  in  the  general  condition  known 
as  "  senile  atrophy." 

More  obscure  forms  of  atrophy  are  those  which  appear  to  be 
occasioned  by  lesions  of  trophic  nerves,  or  are  caused  by  toxic  con- 
ditions ;  e.  g.,  lead-poisoKJr/g. 


CHAPTER  XXII. 
HYPERTROPHY  AND  HYPERPLASIA. 

BY  hypertrophy  is  meant  an  increase  in  the  size  of  the  elements 
composing  a  tissue ;  by  hyperplasia,  an  increase  in  their  number. 
Both  conditions  usually  lead  to  an  enlargement  of  the  organ  in' 
which  they  are  found,  but  this  is  not  necessarily  the  case,  for  all  the 
elements  in  the  organ  need  not  participate  in  the  increase ;  some 
may  diminish  in  bulk. 

1.  Functional  Hypertrophy. — This  process,  like  that  of  functional 
atrophy,  depends  upon  the  activity  of  the  part  undergoing  the 
change.  In  this  case  the  parenchyma  of  the  part  is  increased  to 
meet  a  gradually  increasing  demand  for  the  work  it  is  fitted  to 
perform.  This  increase  may  take  the  form  of  hypertrophy  or  that 
of  hyperplasia.  The  muscular  tissues  meet  the  demand  by  an 
increase  in  the  size  of  the  muscle-cells.  This  is  illustrated  in  the 
hypertrophy  of  the  heart  in  valvular  lesions,  which  throw  extra 
work  upon  the  muscle;  in  the  enlargement  of  the  uterus  during 
gestation,  fitting  it  for  the  strong  contractions  during  labor ;  and 
in  the  enlargement  of  the  voluntary  muscles  by  exercise. 

In  glandular  organs  an  additional  demand  for  work  results  in 
hyperplasia,  in  which  the  epithelial  cells  of  the  parenchyma  multi- 
ply  (Fig.  259). 

Functional  hypertrophy,  or  hyperplasia,  takes  place  only  under 
certain  favorable  conditions.  The  demand  for  extra  functional 
activity  must  not  be  too  great,  otherwise  degenerative  changes 
ensue.  The  same  result  would  follow  were  the  nutritive  supply 
insufficient  to  meet  the  loss  of  material  and  force  sustained  by 
the  cells  in  doing  the  increased  work.  It  is  evident,  then,  that 
the  condition  occasioning  the  hypertrophy  or  hyperplasia  must 
develop  gradually,  and  not  interfere  with  the  supply  of  nutrition. 
The  nature  of  the  tissue  also  influences  the  result.  In  general,  it 
may  be  stated  that  tissues  of  high  specialization  are  less  capable  of 
either  hypertrophy  or  hyperplasia  than  those  less  specialized,  and 
that  hypertrophy  is  the  rule  in  tissues  of  higher  function,  while 

288 


HYPERTROPHY  AND  HYPERPLASIA.  289 

hyperplasia  is  more  common  in  those  of  lower  function,  where  the 
formative  powers  of  the  cells  are  less  in  abeyance. 

COMPENSATORY  HYPERTROPHY  is  a  term  applied  to  functional 
hypertrophy  or  hyperplasia  following  the  destruction  of  an  organ  or 
part  of  an  organ.  This  leads  to  an  increase  of  the  work  demanded  of 
other  parts  capable  of  performing  the  function  normally  carried  on 
by  the  part  destroyed,  or  capable  of  assisting  the  function  that  has 

FIG.  259. 


$3 


Necrosis  of  part  of  an  hepatic  lobule,  (v.  Meister.)  a,  necrosed  cells,  the  nuclei  of  which 
have  lost  their  affinity  for  dyes ;  b,  hypertrophic  cells  with  large  nuclei ;  c,  detritus  of 
blood-corpuscles  in  the  capillaries.  Section  taken  eighteen  hours  after  removal  of  a  por- 
tion of  the  liver  in  a  rabbit.  The  section  is  taken  at  the  margin  between  that  tissue 
which  is  affected  with  necrosis  and  that  which  retains  life,  but  is  stimulated  to  prolifera- 
tion by  the  irritative  effects  of  the  amputation.  After  a  while  the  hypertrophied  epithe- 
lial cells  will  divide  by  karyokinesis  and  attempt  a  restitution  of  the  lost  tissue— a  species 
of  compensatory  hyperplasia. 

suffered  diminution.  Thus,  disease  of  one  kidney  may  indirectly 
occasion  hypertrophy  of  the  other  kidney,  or,  more  properly,  hyper- 
plasia of  its  functional  epithelium,  or  chronic  interstitial  nephritis 
affecting  both  kidneys  may  lead  to  hypertrophy  of  the  heart  by 
throwing  more  labor  upon  that  organ  in  order  that  the  remaining 
renal  parenchyma  may  perform  the  work  demanded  of  the  kidneys. 
In  like  manner  the  auxiliary  muscles  of  respiration  may  become 
hypertrophic  in  cases  of  embarrassed  respiration.1 

Functional  hypertrophy  may  also  find  expression  among  the  con- 

1  Attention  has  already  been  called  to  the  hypertrophies  of  the  hypophysis  and 
parathyroids  in  cases  of  thyroidectomy  or  disease  of  the  thyroid  gland  (see  p.  191). 
19 


290  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

nective  tissues  of  the  body,  in  which  the  usefulness  of  the  tissue 
resides  in  its  physical  properties.  In  muscular  individuals  the  bony 
ridges  giving  attachment  to  the  tendons  are  more  strongly  accen- 
tuated than  in  those  whose  muscles  are  less  highly  developed. 

A  very  familiar  illustration  of  functional  hyperplasia  is  furnished 
by  the  skin  of  the  palms.  Manual  labor  that  is  habitual  occasions 
a  thickening  of  the  epidermis  due  to  hyperplasia  ;  exceptional  over- 
work causes  damage  leading  to  inflammation,  blisters. 

2.  Developmental  Hypertrophy. — Hypertrophy  of  a  part  occasion- 
ally arises  without  assignable  cause  and  apparently  as  a  mere  anomaly 
in  development.     Such  structures  as  horns  and  warts  are  examples 
of  this  form  of  hypertrophy,  which  are  not  readily  separated  from 
the  group  of  growths  called  tumors.     When  the  growth  is  limited 
and  not  progressive  it  may  in  most  cases  be  attributed  to  this  form 
of  hypertrophy ;  when  apparently  unlimited,  progressive,  and  atyp- 
ical in  structure,  it  must  be  classed  among  the  tumors. 

3.  Inflammatory  Hypertrophy. — Under  the  influence  of  damaging 
agents  which  act  with  such  mitigated  intensity  that  their  effect  upon 
the  cells  amounts  merely   to   a  decided   irritation,   the   formative 
powers  of  the  cells  may  be  stimulated  and  an  enlargement  of  the 
part  be  brought  about,  either  as  the  result  of  hypertrophy  or  of 
hyperplasia  of  its  elements.     This  form  of  hypertrophy  is  nearly, 
if  not  quite,  equivalent  to  the  results  of  chronic  productive  inflam- 
mations, for  an  account  of  which  the  student  is  referred  to  another 
chapter.     In  cases  where  the  evidences  of  damage  are  inappreciable 
the  process  may  be  considered  as  irritative  hypertrophy  or  hyper- 
plasia ;  where  they  are  at  all  marked,  it  must  be  regarded  as  inflam- 
matory. 

The  microscopical  evidence  of  hypertrophy  is  found  in  an  increase 
of  size  in  the  elements  composing  the  tissue.  It  is  not  a  simple 
matter  to  decide  from  a  microscopical  examination  whether  hyper- 
plasia exists  or  not,  for  the  microscopical  appearances  are  almost,  if 
not  quite,  normal.  It  is  often  necessary  to  consider  the  changes  in 
the  gross  appearances  of  the  part  in  order  to  determine  whether  its 
constituent  elements  have  increased  in  number  or  not. 


CHAPTER  XXIII. 
METAPLASIA. 

WHEN  a  fully  developed  tissue  becomes  modified  in  its  structure 
to  resemble  another  form  of  adult  tissue,  without  passing  through 
an  intermediate  stage  of  indifferent  or  more  embryonic  tissue,  the 
process  is  known  as  "  metaplasia."  It  differs  from  the  inflammatory 
process  in  that  the  rejuvenescence  of  the  tissue  is  not  obvious,  and 
it  is  unlike  the  development  of  a  tumor  because  the  tissue-change 
is  a  conversion  of  one  form  of  tissue  into  another,  and  not  the  pro- 
duction of  a  new  tissue  within  another. 

Metaplasia  only  results  in  the  formation  of  a  tissue  closely  allied 
to  that  in  which  it  takes  place.  It  is  most  commonly  met  with  in 
the  connective  tissues,  where  a  change  in  the  character  of  the  inter- 
cellular substances  and  in  the  form  of  the  cells,  which  all  spring 
from  the  same  original  source,  the  mesoderm,  is  all  that  is  necessary 
to  convert  one  form  of  connective  tissue  into  another  variety  of 
the  same  group.  We  must  attribute  the  change  to  a  modification 
in  the  functional  activity  of  the  cells,  the  reasons  for  which  are  in 
most  cases  very  obscure.  We  may,  perhaps,  in  some  cases,  seek 
the  explanation  in  conditions  that  lead  to  an  altered  functional 
demand  on  the  part.  Thus,  for  example,  it  has  been  noticed  that 
bone  sometimes  develops  in  the  fibrous  tissues  of  the  thigh  or 
shoulder  in  soldiers  that  are  obliged  to  ride  or  carry  a  musket  for  a 
long  time.  It  may  be  that  the  fibrous  tissue  becomes  reinforced  in 
these  cases  with  bone,  because  it  is  better  calculated  to  withstand 
the  pressure ;  but  the  fact  that  such  cases  are  exceptional  shows 
that  this  response  on  the  part  of  the  tissues  is  by  no  means  con- 
stant and  that  the  explanation  is  incomplete. 

Metaplasia  may  result  in  the  conversion  of  fibrous  tissue  into 
mucous  or  osseous  tissue ;  hyaline  cartilage  into  fibro-cartilage,  or 
into  fibrous,  mucous,  or  osseous  tissue ;  adipose  tissue  into  mucous 
tissue,  etc.  The  metaplastic  tissue  is  usually  not  typical ;  that  is, 
it  differs  somewhat  from  the  normally  developed  tissue  in  the  finer 
details  of  its  structure.  Thus,  the  bone  that  is  produced  by  meta- 

291 


292  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

plasia  from  fibrous  tissue  lacks  the  elaborate  system  of  canaliculi 
that  is  found  in  normally  developed  osseous  tissue,  although  in  its 
essential  features  it  is  virtually  bone,  the  intercellular  substances 
being  impregnated  with  calcareous  matter  and  yielding  gelatin  on 
boiling. 

Epithelial  tissues  may  also  be  the  seat  of  metaplasia.  Under  the 
influence  of  moderate  but  repeated  damage,  columnar  epithelium 
may  become  modified  into  a  stratified  variety.  In  such  cases  the 
cause  may,  presumably,  be  traced  to  a  change  of  conditions,  which 
calls  for  an  unusual  exercise  of  the  protective  function  of  the  epi- 
thelium. The  uterine  cavity  and  the  respiratory  tract  are  the  most 
common  situations  in  which  this  transformation  of  epithelium  is 
met  with.  A  similar  conversion  of  transitional  epithelium  into  true 
stratified  epithelium  is  occasionally  met  with  in  the  bladder  and 
renal  pelvis,  as  the  result  of  a  calculus  not  causing  sufficient  damage 
to  induce  an  active  inflammation. 

Metaplasia  appears  to  result  from  a  change  in  the  functional 
activities  of  the  cells,  which  lose  their  accustomed  form  of  special- 
ization and  acquire  new  ones  of  closely  related  character. 


CHAPTER   XXIV. 

STRUCTURAL  CHANGES  DUE  TO  AND  FOLLOWING 

DAMAGE. 

I.  NECROSIS. 

THE  term  necrosis  designates  a  local  death  of  tissue  during  the 
life  of  the  individual. 

In  our  study  of  the  normal  tissues  under  the  microscope  we  are 
obliged  to  use  methods  of  preparation  which,  in  nearly  all  cases, 
kill  the  tissues  before  they  come  under  observation.  When  we 
examine  them  with  a  view  to  determining  their  structure,  they  are 
nearly  always  necrotic,  if  we  may  use  that  term  in  this  connection. 
Our  standards  of  the  normal  appearances  are,  therefore,  largely 
based  upon  what  we  learn  from  recently  killed  tissues. 

In  some  instances  it  is  possible,  however,  to  examine  even  highly 
developed  tissues  while  still  living.  If,  for  example,  the  super- 
ficial layer  of  a  frog's  cornea  be  stripped  off  and  mounted  in  a 
drop  of  serum,  the  cells  composing  it  may  be  readily  seen  under  the 
microscope.  While  such  a  preparation  is  quite  recent  it  is  difficult 
to  distinguish  clearly  the  nuclei  within  the  cells,  their  refractive 
indices  being  nearly  the  same  as  that  of  the  surrounding  cyto- 
plasm ;  but  in  a  short  time  the  nuclei  suddenly  become  very  distinct, 
as  though  they  had  undergone  a  sort  of  crystallization.  This  is 
probably  an  indication  of  the  death  of  the  nuclei,  the  substances 
composing  them  having  suffered  a  coagulation  which  increases  their 
powers  of  refracting  light  and,  in  consequence,  the  distinctness  with 
which  they  are  seen.  This  conclusion  is  strengthened  by  the  fact 
that  the  change  may  be  hastened  by  the  application  of  reagents,  such 
as  acetic  acid. 

The  modern  methods  of  preparation  used  in  histological  studies 
aim  at  bringing  about  a  sudden  death  of  the  cells  and  such  a  coag- 
ulation of  the  tissue-elements  as  shall  prevent  further  changes  of 
structure  before  the  tissues  can  be  studied.  For,  if  the  tissues  are 
allowed  to  die  spontaneously,  their  elements  suffer  changes  that 
greatly  alter  their  appearance.  When  they  die  and  remain  within 

293 


294  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

the  living  body,  as  is  the  case  in  necrosis,  those  changes  in  structure 
are  more  diverse  and  more  marked  than  those  incident  to  spontaneous 
death  resulting  from  removal.  This  has  led  to  the  distinction  of 
several  varieties  of  necrosis,  characterized  by  different  structural 
changes  in  the  dead  tissue,  which  are  dependent  upon  the  conditions 
obtaining  in  the  tissue  at  the  time  of  death  or  after  death  has  taken 
place. 

Among  the  most  striking  changes  incident  to  necrosis  are  those 
affecting  the  nucleus.  This  may  retain  its  form  in  great  measure, 
but  lose  its  affinity  for  the  nuclear  dyes  ("  chromolysis,"  Fig.  262), 
or  the  chromoplasmic  substances  may  retain  that  affinity,  but  be 
broken  up  into  fragments,  thus  destroying  the  form  of  the  nucleus 
("  karyolysis,"  Figs.  260  and  261).  Both  of  these  changes  are 
indicative  of  the  death  of  the  nucleus  and  assure  the  death  of 
all  parts  of  the  cell. 

FIG.  260.  FIG.  261.  FIG.  262. 


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Changes  in  the  nuclei  of  renal  epithelial  cells  incident  to  necrosis.    (Schmaus.) 
Fig.  260.— Destruction  of  the  chromatic  reticulum  and  condensation  of  the  chromatin  in 

masses  of  various  sizes ;  early  stage  of  karyolysis.    Nuclear  membrane  nearly  gone. 
Fig.  261. — More  advanced  stage  of  nuclear  destruction.  The  nuclear  fragments  lie  free  in  the 

cytoplasm ;  later  stage  of  karyolysis. 

Fig.  262.— Disintegration  and  disappearance  of  the  chromatin  without  a  coincident  disinte- 
gration of  the  form  of  the  nucleus-chromolysis. 

1.  Coagulation-necrosis. — When  the  tissues  that  have  suffered 
death  liberate  fibrinoplastic  substances  and  fibrin-ferment  these 
interact  with  the  fibrinogen  in  the  lymph  and  occasion  a  coagula- 
tion of  the  necrosed  tissue  analogous  to  the  production  of  fibrin. 
These  coagulated  materials  may  appear  as  fine  granules  or  as 
hyaline  masses  of  a  dense,  glassy  character.  This  form  of  necrosis 
is  illustrated  in  the  formation  of  the  "  membrane "  in  diphtheria, 
which  is  the  superficial  portion  of  the  affected  part  that  has  under- 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE. 


295 


gone  coagulation-necrosis  (Fig.  263).  When  the  granular  form  of 
coagulation-necrosis  is  associated  with  albuminoid  and  fatty  degen- 
eration the  result  is  a  cheese-like  mass,  and  the  process  is  known 
as  cheesy  degeneration  (p.  274). 

2.  Colliquative  Necrosis  (Fig.  281). — This  form  of  necrosis  is  fol- 
lowed by  an  imbibition  of  fluid,  occasioning  a  disintegration  of  the 

FIG.  263. 


/    .  e 

Edge  of  a  diphtheritic  membrane.  Section  from  the  human  uvula.  (Ziegler.)  a,  normal 
stratified  epithelium ;  b,  subepithelial  fibrous  tissue  of  the  mucous  membrane  ;  c,  epithe- 
lium that  has  undergone  coagulation-necrosis.  Only  remnants  of  cells  remain  in  the 
coarse  fibrinous  meshwork.  d,  oedematous  subepithelial  fibrous  tissue  containing  fibrin 
and  leucocytes ;  e,  bloodvessels;  /,  haemorrhage ;  g,  g,  groups  of  the  bacteria  causing  the 
necrosis. 

tissue-elements,  which  are  broken  up  into  a  granular  detritus  sus- 
pended in  the  fluid. 

The  foregoing  two  forms  of  necrosis  may  be  associated  with  each 
other,  or  one  may  follow  the  other. 

The  fate  of  the  necrosed  tissue  depends  upon  a  variety  of  circum- 
stances. The  presence  of  dead  tissue  excites  an  inflammation  in 
the  living  tissue  surrounding  it,  and  the  character  of  this  inflam- 
mation often  determines  the  fate  of  the  necrosed  mass.  (See  article 
on  inflammation.)  The  situation  of  the  dead  tissue  also  affects  the 
result.  The  following  examples  will  serve  to  illustrate  these  vari- 
ations : 

1.  ABSORPTION. — The  necrosed  tissue-elements  become  disin- 
tegrated, and  the  debris  either  dissolved  or  carried  away  through 
the  lymphatic  channels  by  the  currents  of  fluid,  or  through  the 


296  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

agency  of  leucocytes,  which  incorporate  them  and  then  pass  out  of 
the  necrotic  area.  This  disintegration  appears  to  be  due  partly  to 
a  simple  maceration  or  separation  of  the  particles  of  the  tissue, 
partly  to  a  solvent  action  exerted  by  the  fluids  in  the  tissues  upon 
dead  organic  matter.  While  absorption  is  going  on  there  is  an 
inflammatory  reaction  in  the  surrounding  tissues  that  still  retain 
life,  which  results  in  the  formation  of  cicatricial  tissue.  This  may 
ultimately  occupy  the  site  of  the  necrosed  tissue,  or  it  may  form  a 
capsule  around  a  collection  of  fluid  occupying  that  site,  the  result 
being  a  cyst  with  a  fibrous  wall. 

2.  ENCAPSULATION. — The   necrosed  tissues  may  remain   unab- 
sorbed,  or  be  only  partly  absorbed,  and  eventually  become  enclosed 
in  a  capsule   of   new-formed   fibrous   tissue    arising   through   the 
inflammatory  process  mentioned  above.     In  this  case  the  necrosed 
mass  becomes  desiccated  through  absorption  of  its  fluid  constituents, 
and  may  eventually  be  infiltrated  with  lime-salts,  calcified. 

3.  GANGRENE. — This  occurs  in  two  forms,  distinguished  as  dry 
and  moist  gangrene. 

Dry  gangrene  is  due  to  the  desiccation  of  dead  tissues  that  are 
exposed  to  the  air.  The  tissues  become  discolored,  owing  to  changes 
in  the  coloring-matter  of  the  blood,  and  shrink,  the  skin  assuming 
the  appearance  of  parchment.  After  a  time  the  dead  mass  is  cast 
off  by  the  formation  of  granulation-tissue  from  the  neighboring 
living  tissues. 

Moist  gangrene  is  the  result  of  putrefactive  changes  in  dead 
tissue,  due  to  infection  with  bacteria  causing  decomposition.  The 
parts  are  discolored,  swollen,  moist,  and  often  contain  bubbles  of 
gas  having  a  foul  odor.  The  gangrenous  part  may  here  also  be 
cast  off  as  the  result  of  the  formation  of  granulations,  but  the 
gangrenous  process  may  spread  before  it  can  be  checked  by  an 
inflammatory  demarcation,  the  products  of  decomposition  having 
a  poisonous  effect  upon  the  neighboring  tissues  that  leads  to  necrosis 
and  prevents  the  development  of  granulation-tissue. 

4.  SUPPURATION. — If  the  dead  matter  contain  pyogenic  micro- 
organisms, they  exert  a  peptonizing  action  upon  the  necrotic  mass, 
causing  it  to  liquefy.     At  the  same  time  they  excite  a  purulent 
inflammation  in  the  surrounding  tissues  which  leads  to  the  forma- 
tion of  an  abscess  or  an  ulcer. 

In  those  cases  of  necrosis  in  which  the  necrosed  tissues  are  not 
speedily  absorbed  the  dead  mass  is  known  as  a  "  sequestrum,"  and 


STRUCTURAL   CHANGES  DUE  TO  DAMAGE.  297 

the  zone  of  inflammation  separating  it  from  the  living  tissues  is 
called  the  line  or  plane  of  demarcation.  (For  a  fuller  explanation 
of  the  process  of  demarcation  and  of  the  tissue-changes  that  lead 
to  encapsulation,  the  student  is  referred  to  the  article  on  inflamma- 
tion.) 

II.  INFLAMMATION. 

It  is  difficult  to  frame  an  accurate  definition  of  inflammation,  for 
the  reason  that  the  term  includes  a  number  of  different  conceptions 
that  cannot  be  readily  expressed  in  concise  form.  In  general,  it 
may  be  stated  that  inflammation  is  a  process  of  repair  following  a 
limited  damage  to  the  tissues.  The  injurious  agent  acting  upon  a 
part  must  inflict  a  certain  amount  of  damage  in  order  to  bring 
about  inflammation  :  if  its  action  be  slight,  it  will  cause  only  an 
evanescent  irritation  which  does  not  pass  into  inflammation  ;  if, 
on  the  other  hand,  its  action  be  severe,  it  occasions  necrosis  or 
degenerative  changes  at  the  point  of  its  application,  and  only  in 
remoter  parts  of  the  tissue,  where  its  action  is  moderate,  will 
inflammatory  changes  be  manifested.  The  nature  of  the  damaging 
cause  and  that  of  the  tissues  affected  both  influence  the  character  of 
the  inflammatory  process.  It  therefore  manifests  many  variations 
under  different  circumstances,  and  in  order  to  understand  the 
underlying  principles  of  the  process  it  will  be  best  to  select  some 
particular  example  for  a  somewhat  close  study,  and  then  to  consider 
some  of  the  circumstances  that  modify  the  phenomena  presented  by 
that  example.  A  severe  burn,  the  effects  of  which  extend  deeply 
enough  to  destroy  a  part  of  the  true  skin,  will  serve  this  purpose,  as 
affording  an  example  of  acute  inflammation  of  a  vascularized  part 
following  a  cause  that  has  acted  for  only  a  short  time  and  has  then 
been  removed. 

In  considering  this  example  we  must  distinguish  between  those 
destructive  effects  that  are  due  to  the  damaging  cause,  and  the 
reparative  processes  that  follow  in  the  tissue-elements  that  have 
been  less  seriously  affected.  It  will  make  the  example  clearer  if 
we  also  separately  consider  the  phenomena  presented  by  the  vascular 
system  from  those  taking  place  in  the  fixed  tissues  of  the  part 
exclusive  of  the  bloodvessels. 

Those  tissues  which  have  come  into  the  closest  contact  with  the 
source  of  heat  will  have  been  quickly  killed  and,  perhaps,  charred. 
Beyond  this  point  of  complete  destruction  the  tissues  may  be  roughly 


298  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

divided  into  zones,  in  which  the  direct  damage  is  successively  less 
marked.  In  the  first  zone  necrosis  will  have  taken  place ;  in  the 
tissues  that  are  more  remote,  degenerative  changes  will  be  occa- 
sioned ;  and  still  farther  away  from  the  seat  of  injury  the  tissues 
will  show  a  vital  reaction  to  the  stimulation  or  irritation  they  have 
received,  which  will  reveal  itself  in  a  growth,  eventually  leading  to 
a  repair  or  patching  of  the  defect  in  the  tissues  occasioned  by  the 
damage. 

1.  The  Bloodvessels  and  the  Circulation. — The  vessels  most  seri- 
ously damaged,  together  with  the  blood  they  contained,  will  have 
been  completely  destroyed  ;  in  those  less  affected  the  circulation 
will  have  been  arrested  and  the  blood  coagulated.  But  beyond  the 
zones  in  which  the  function  of  the  circulation  has  been  abolished  the 
first  marked  effect  is  an  increase  in  the  volume  and  rapidity  of  the 
current  of  blood.  This  increased  flow  of  blood  to  the  part  is 
attributed  to  the  action  of  the  injury  upon  the  vaso-motor  system 
of  nerves,  causing  a  relaxation  of  the  walls  of  the  arteries'  supply- 
ing the  part  which  has  been  damaged.  A  similar  increase  in  circu- 
lation follows  slighter  stimulation  of  the  skin,  as,  e.  g.,  rubbing,  so 
that  this  determination  of  blood  to  the  part  as  the  result  of  vaso- 
motor  disturbance  is  comparable  with  entirely  normal  hypersemias ; 
but  it  is  greater  in  degree  when  the  irritation  of  the  parts  is  great 
enough  to  cause  damage. 

After  an  interval  the  velocity  of  the  circulation  in  the  part  which 
is  becoming  inflamed  is  reduced,  without  any  diminution  in  the 
calibre  of  the  vessels,  and  the  slackening  of  the  current  may  pass 
into  complete  stasis.  This  is  probably  due  to  two  causes  :  first,  to 
the  extension  of  the  vaso-motor  disturbance  beyond  the  area  of  the 
injured  part,  so  that  collateral  branches  of  the  main  arteries  are 
dilated ;  this  would  diminish  the  pressure  of  blood  going  to  the 
inflamed  part.  Second,  to  alterations  in  the  walls  of  the  smaller 
vessels  in  the  inflamed  part,  especially  the  capillaries  and  small  veins. 
These  become  more  pervious,  probably  as  the  result  of  the  damage 
they  have  sustained  in  common  with  the  other  tissues,  allowing  a 
greater  amount  of  fluid  to  pass  through  them  than  when  they  were 
in  the  normal  condition.  This  comparatively  rapid  extraction  of 
its  watery  constituent  increases  the  viscosity  of  the  blood,  and  that 
increased  viscosity,  together  with  the  changes  in  the  walls  of  the 
vessels,  increases  the  friction  between  the  two,  impeding  the  cir- 
culation. 


STRUCTURAL   CHANGES  DUE  TO  DAMAGE. 


299 


Thus,  two  influences  appear  to  check  the  flow  of  the  blood  after 
the  inflammatory  process  has  been  inaugurated  :  (1)  a  diminution 
of  the  pressure  urging  the  blood  forward,  and  (2)  an  increase  in  the 
resistance  offered  to  the  passage  of  the  blood  through  the  smaller 
vessels.  To  these,  another  factor  increasing  the  resistance  is  added 
as  soon  as  the  current  has  become  slowed  beyond  a  certain  point. 
During  the  normally  rapid  flow  of  the  blood  the  corpuscles  it  con- 
tains, being  heavier  than  the  serum,  form  a  column  in  the  axis  of 
the  vessels,  with  a  clear  zone  of  serum  around  it  (Fig.  264).  This  is 
in  accordance  with  the  physical  laws  governing  the  behavior  of  sus- 
pended particles  in  fluids  circulating  in  a  tube ;  but  if  the  rate  of 
flow  be  diminished  beyond  a  certain  point,  the  suspended  particles 

FIG.  264. 


FIG.  265. 


.1 


FIG.  266. 


c  d 

Positions  of  the  corpuscles  in  circulating  blood.    (Eberth  and  Schimmelbusch.) 

Fig.  264.— Appearance  when  the  velocity  of  the  circulation  is  normal :  a,  axial  column  of 
corpuscles,  both  red  and  white,  in  such  rapid  movement  that  individual  corpuscles  can- 
not be  distinguished.  Occasionally  a  white  corpuscle  is  thrown  from  the  axial  mass  and 
appears  in  the  plasmic  zone,  b. 

Fig.  265.— Appearance  when  the  velocity  of  the  circulation  is  moderately  reduced.  The 
zone  b  contains  numerous  leucocytes. 

Fig.  266.— Appearance  when  the  current  of  blood  is  sluggish:  a,  red  corpuscles,  still  in  the 
axis  ;  b,  peripheral  zone,  containing  leucocytes,  d,  and  blood-plates,  c. 

When  stasis  is  fully  established  the  red  corpuscles  also  invade  the  peripheral  zone. 

The  figures  are  from  observations  made  on  the  vessels  of  a  dog's  omentum  during  life. 

invade  the  fluid  zone  at  the  periphery  of  the  current,  those  which  are 
specifically  most  nearly  of  the  same  weight  as  the  fluid  passing 
most  freely  into  it.  In  the  case  of  the  blood  those  particles  are  the 
leucocytes,  which  are  lighter  than  the  red  corpuscles,  and,  as  the 


300  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

current  slackens,  it  is  these  which  first  make  their  way  into  the  clear 
serum  at  the  periphery  of  the  stream  and  soon  come  in  contact  with 
the  vascular  wall  (Figs.  265  and  266).  Here,  by  virtue  of  their 
adhesiveness,  they  cling  to  the  endothelium,  and  must  materially 
increase  the  difficulty  with  which  the  blood  is  forced  forward  and 
promote  stasis. 

While  the  blood  is  circulating  freely  in  the  vessels  the  leucocytes 
it  contains  are  subjected  to  repeated  mechanical  shocks  through 
contact  with  other  corpuscles  or  with  the  walls  of  the  vessels 
where  these  branch  or  form  sharp  curves.  These  blows  cause  the 
cytoplasm  to  contract,  maintaining  the  globular  form  of  the  cor- 
puscle ;  but  when  they  come  to  rest  upon  the  surface  of  the  vascular 
wall,  as  may  occasionally  happen  under  normal  circumstances,  and 
is  always  the  case  in  acute  inflammations,  the  leucocytes  have  an  op- 
portunity to  execute  the  movements  which  have  been  called  "  amoe- 
boid/7 from  their  resemblance  to  those  displayed  by  the  amoeba. 
The  leucocytes  send  out  pseudopodial  processes  and  creep  along  the 
surface  of  the  vessel-wall.  We  must  bear  in  mind  that  at  this 
time  the  capillary  vessels  are  dilated,  and  that  the  cement  between  the 
endothelial  cells  is  somewhat  stretched  and  thinned.  The  passage 
of  the  pseudopodia  of  the  leucocytes  through  the  cement  is  facilitated 
by  these  circumstances,  so  that  soon  after  the  circulation  has  become 
slowed  there  is  a  passage  of  leucocytes  through  the  walls  of  the  ves- 
sels into  the  spaces  in  the  surrounding  tissues.  This  escape  of  the 
leucocytes  is  called  their  "emigration"  (Fig.  267).  The  number 

FIG.  267. 

5 


Emigration  of  leucocytes  through  a  capillary  wall.  (Engelmann.)  a.  leucocyte  just  leaving 
one  of  the  pseudostomata  between  the  endothelial  cells  of  the  capillary  wall ;  6,  leucocyte1 
partly  within  and  partly  outside  of  the  capillary ;  c,  nucleus  of  an  endothelial  cell  of  the 
capillary  wall. 

of  leucocytes  that  escape  from  the  blood  in  the  manner  described  is 
variable.  In  some  varieties  of  inflammation  the  tissues  outside  of 
the  vessels  contain  substances  that  have  an  attraction  for  the  leuco- 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE.  301 

eytes.  This  is  particularly  the  case  when  the  cause  of  the  inflam- 
mation is  an  infection  with  bacteria.  Under  those  circumstances 
the  leucocytes  that  emigrate  from  the  blood  accumulate  in  great 
numbers  in  the  tissues  around  the  site  of  infection. 

The  leucocytes,  by  their  passage  through  the  cement  between  the 
endothelia,  open  minute  channels  through  which  the  red  corpuscles 
of  the  blood  may  be  pressed  into  the  surrounding  tissues,  when  they 
come  in  contact  with  the  vascular  wall  after  stasis  (complete  arrest 
of  the  circulation)  has  become  established.  These  corpuscles  are 
soft,  and  can  be  forced  through  orifices  much  smaller  than  their 
normal  diameters;  but  the  number  that  escape  from  the  vessels 
varies  greatly  in  different  cases  of  inflammation,  and  it  is  probable 
that  the  integrity  of  the  vascular  wall  is  more  affected  when  the 
number  is  great  than  when  it  is  slight,  and  that  the  leucocytes 
prepare  the  way  for  only  a  portion  of  the  red  corpuscles  that  escape 
from  the  vessel  in  those  cases  in  which  large  numbers  pass  into  the 
surrounding  tissues.  The  escape  of  red  corpuscles  from  a  vessel 
without  obvious  rupture  of  its  walls  is  called  "  diapedesis." 

As  a  result  of  the  processes  already  described,  it  will  be  observed 
that  three  of  its  constituents  pass  from  the  blood  into  the  sur- 
rounding tissues  :  (1)  serum,  (2)  leucocytes,  and  (3)  red  blood-cor- 
puscles. These  constitute  what  is  known  as  the  u  exudate."  But 
to  these  three  a  fourth  constituent  is  soon  added,  namely,  fibrin. 
The  formation  of  fibrin  is  still  awaiting  a  perfectly  clear  explana- 
tion, but  it  is  usually  assumed  to  be  the  result  of  the  interaction  of 
three  substances  :  (1)  fibrinogen,  derived  from  the  plasma  of  the 
blood  ;  (2)  fibrinoplastin  and  (3)  fibrin-ferment,  both  of  which  may 
come  from  the  bodies  of  cells.  In  the  exudate  of  acute  inflamma- 
tion all  of  these  elements  necessary  for  the  formation  of  fibrin  are 
present  in  greater  or  less  amount.  (See  explanation  of  fibrin- 
formation  on  p.  127.)  As  found  in  the  tissues,  therefore,  the  exu- 
date consists  of  serum,  fibrin,  leucocytes,  and  red  corpuscles  (Fig. 
268).  But  in  different  cases  their  relative  abundance  differs,  and 
the  acute  inflammations  have  been  roughly  classified  according  to 
the  character  of  the  exudate.  Thus,  the  serous  inflammations  are 
those  in  which  serum  predominates  in  the  exudate.  In  like 
manner  inflammations  are  designated  by  the  terms  fibrinous, 
hsemorrhagic,  and  purulent  (when  the  leucocytes  predominate),  or 
sero-fibrinous,  sero-purulent,  fibrino-purulent,  etc.  These  terms 
are  descriptive,  and  merely  indicate  variations  in  the  proportions 


302 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


of 'the  different  constituents  in  the  extidate.     The  general  nature 
of  the  process  is  the  same  in  all  cases. 

We  are  now  in  a  position  to  explain  four  of  the  cardinal  symp- 
toms of  acute  inflammation.  The  increase  of  temperature  and  the 
redness  (calor  and  rubor)  are  attributable  to  the  hypersemia  of  the 
part  and  its  surroundings.  The  swelling  and  pain  (tumor  and 
dolor)  are  caused,  at  least  chiefly,  by  the  presence  of  the  exudate. 
The  suspension  of  function,  or  fifth  cardinal  symptom  of  acute 

FIG.  268. 


d  e     f 

Section  from  lung  in  the  second  or  exudative  stage  of  croupous  pneumonia :  a,  endothelial 
wall  of  a  small  vein ;  &,  blood  within  the  vein,  unusually  rich  in  leucocytes,  which  have 
collected  during  the  slowing  of  the  circulation.  The  line  6  points  to  the  nucleus  of  a 
leucocyte.  Part  of  the  blood  has  fallen  out  of  the  section  during  its  preparation,  c,  leu- 
cocytes beneath  the  endothelixim  of  the  vascular  wall ;  d,  cedematous  fibrous  tissue  sur- 
rounding the  vessel.  The  fibres  of  the  tissue  have  been  separated  by  the  exuded  serum. 
This  tissue  is  also  moderately  infiltrated  with  leucocytes  that  may  have  passed  through 
the  walls  of  the  vein,  and  contains  a  few  red  blood-corpuscles,  e,  wall  separating  two  pul- 
monary alveoli.  This  is  also  somewhat  infiltrated  with  leucocytes.  /,  exudate  within  an 
alveolus,  consisting  of  serum,  fibrin,  leucocytes,  and  red  blood-corpuscles ;  it  also  con- 
tains a  few  epithelial  cells  desquamated  from  the  alveolar  wall,  g. 

inflammation,  may  have  a  more  complex  causation.  It  may  be  due 
to  the  immediate  effects  of  the  injury  that  occasioned  the  inflam- 
mation, to  disturbance  of  nutrition,  to  the  presence  of  the  exudate, 
or  perhaps  to  an  interruption  of  the  normal  nervous  mechanism. 
All  these  disturbing  factors  are  present,  and  may  vary  in  their 
potency  in  different  cases. 

All  the  changes  that  have  been  hitherto  described  are  the  imme- 
diate or  only  slightly  remote  effects  of  the  damage  to  the  tissues, 
and  have  nothing  to  do  with  the  process  of  repair.  They  may  be 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE.  303 

regarded  as  constituting  the  destructive  phase  of  acute  inflamma- 
tion. 

2.  The  Fixed  Elements  of  the  Tissues. — It  is  evident  that  the 
cause  of  damage  itself,  or  the  disturbances  of  nutrition  resulting 
from  the  changes  in  the  circulation,  must  either  cause  rapid  death, 
necrosis,  or  that  slower  form  of  death  entailed  by  a  relatively  in- 
sufficient supply  of  nourishment,  which  has  been  described  in  the 
chapter  on  the  degenerations.  The  cells  are  either  killed  at  once,  or 
are  starved  within  a  certain  radius  of  the  point  at  which  the  cause 
of  the  inflammation  was  applied.  Beyond  this  radius  these  changes 
give  place  to  those  that  bring  about  repair.  But  the  susceptibility 
of  the  different  tissue-elements  varies :  an  injury  that  would  kill 
some  might  hardly  affect  others ;  a  given  degree  of  innutrition 
might  cause  degeneration  in  some  and  not  in  others,  so  that  the 
depth  to  which  those  changes  are  felt  will  depend  upon  the  nature 
of  the  tissues  present.  In  general,  it  may  be  stated  that  those  tis- 
sues which  are  highly  specialized  and  those  which  carry  on  functions 
requiring  active  intracellular  metabolism  are  the  ones  most  deeply 
affected  by  damaging  influences. 

Repair. — The  view  was  at  one  time  strongly  upheld  that  emi- 
grated leucocytes  were  active  in  the  formation  of  the  new  tissues 
that  developed  during  inflammation.  These  corpuscles  were  re- 
garded as  of  indifferent  character,  capable  of  differentiation  into 
the  various  forms  of  connective  tissue.  This  view  has  not  been 
supported  by  the  results  of  experimental  study,  and  is  now  aban- 
doned, giving  place  to  a  revival  of  the  earlier  belief  that  the  cells 
of  the  fixed  tissues  are  the  active  elements  in  the  reparative  process 
which  results  in  the  formation  of  new  tissues. 

Since  the  significance  of  the  mitotic  figures  during  karyokinesis 
has  been  learned,  it  has  become  possible  to  ascertain  positively  that 
the  fixed  cells  multiply  beyond  the  zone  of  destruction  in  acute 
inflammations.  The  cells  \vhich  have  suffered  neither  destruction 
nor  degeneration  beyond  their  powers  of  recuperation  undergo  a 
species  of  rejuvenescence,  returning  to  a  comparatively  undiffer- 
entiated  condition,  in  which  their  powers  of  reproduction  and  tissue- 
formation  are  revived.  It  is  as  though  they  reverted,  under  the 
influence  of  strong  irritation,  to  the  condition  in  which  their  pro- 
genitors existed  at  an  earlier  stage  of  tissue-development.  The 
process  of  repair  depends  upon  this  capacity  for  rejuvenescence  on 
the  part  of  the  cells  of  the  tissues,  but  that  power  varies  greatly  in 


304  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

the  cells  of  different  tissues,  being,  roughly,  inversely  proportional 
to  the  degree  of  specialization  to  which  they  have  attained.  Those 
tissues  whose  functional  activities  in  the  adult  are  chiefly  formative 
possess  this  capacity  for  rejuvenescence  in  a  high  degree.  In  fact, 
epithelium  in  many  situations — e.  g.,  upon  the  skin — merely  requires 
a  little  stimulation  of  its  normal  activities  to  produce  new  tissue. 
The  case  is  different  with  tissues  of  higher  function,  in  which  the 
cells  have  become  greatly  specialized  at  a  sacrifice  of  their  formative 
activities.  In  these  the  capacity  for  rejuvenescence  is  always  com- 
paratively slight,  and  may  be  entirely  lost ;  as,  for  example,  in  the 
ganglion-cells  of  the  central  nervous  system.  Such  parenchymatous 
cells  of  high  function  are  also  more  vulnerable  than  cells  of  a  lower 
type  of  specialization,  because  they  are  more  dependent  for  their 
functional  activity  upon  a  maintenance  of  the  normal  conditions  of 
nutrition. 

The  foregoing  considerations  explain  why  the  more  highly  spec- 
ialized cells  are  damaged  for  a  greater  distance  from  the  point  of 
injury  than  are  the  connective-tissue  cells,  and  also  why  they  play 
a  less  prominent  part  in  the  restorative  processes  that  follow  those 
which  have  been  destructive.  The  result  is  that  the  zone  of  con- 
nective tissue  capable  of  rejuvenescence  is  nearer  to  the  site  of 
injury  than  the  zone  which  includes  undegenerated  cells  of  higher 
function,  and  from  this  it  follows  that  the  defects  in  the  tissues  are 
made  good  by  a  proliferation  of  connective  tissue,  accompanied  in 
only  slight  degree  by  a  proliferation  or  restitution  of  the  tissues  of 
greater  specialization.  The  process  of  repair  is  more  a  patching 
of  the  defect  than  a  restoration  of  the  normal  structure.  It  results 
in  a  permanent  scar,  and  not  the  perfect  replacement  of  lost  tissues 
by  others  of  the  same  structure  and  function. 

During  rejuvenescence  the  cells  of  the  connective  tissues  enlarge 
and  become  more  cytoplasmic,  and  their  nuclei  become  richer  in 
chromatin.  They  then  divide  by  the  indirect  process,  giving  rise 
to  a  number  of  spheroidal  cells,  which,  together  with  newly  devel- 
oped loops  of  capillary  bloodvessels,  constitute  an  undifferentiated 
tissue,  called  "  granulation-tissue."  During  its  formation  at  least  a 
part  of  the  original  fibrous  intercellular  substance  appears  to  be  re- 
moved by  absorption.  This  may  be  brought  about  by  maceration  in 
the  fluids  present,  or  through  the  agency  of  the  leucocytes  that  have 
emigrated  from  the  vessels  and  play  the  part  of  phagocytes  (Fig.  269). 

The  young  vascular  loops  that  supply  the  granulation-tissue  are 


STRUCTURAL  CV/.1AV, '/•;>>'  /H7<:  TO  DAMAGE. 


305 


FIG.  -2W. 


*  if£    » 

*'  V' 


!*•• 

c 


Section  from  adipose  tissue  in  the  neighborhood  of  a  phlegmonous  inflammation  due  to 
infection  with  streptococci.  (Grawitz.)  F,  the  boundaries  of  fat-cells,  the  tissue  repre- 
sented being  the  connective  tissue  between  those  cells.  Four  large  karyokinetic  figures 
are  seen  in  that  tissue ;  these  are  in  the  rejuvenescent  cells  of  the  fibrous  tissue.  The 
section  also  contains  leucocytes  that  have  wandered  into  the  tissue  from  the  neighbor- 
ing focus  of  exudation.  These  are  designated  by  the  letters  L  and  c.  Ci  and  c2  are  con- 
nective-tissue cells  undergoing  destruction,  their  nuclei  showing  chromolysis.  Other 
connective-tissue  cells  show  a  swelling  of  the  nucleus  (karyolysis),  and  the  interstitial 
tissue  is  the  seat  of  a  moderate  oadema. 

produced  through  a  similar  rejuvenescence  of  the  endothelial  cells 
of  the  older  capillaries.  Those  cells  become  richer  in  cytoplasm, 
and  acquire  a  strong  resemblance  to  epithelial  cells  (Fig.  270). 
They  then  multiply,  forming  little  collections  of  cells  in  contact  at 

FIG.  270. 


Sections  from  granulations  forty-eight  hours  old.  (Nikiforoff.)  In  both  A  and  B  two  capil- 
laries are  represented,  a,  young  connective-tissue  cell ;  a\,  karyokinetic  figures  in  such 
cells;  6,  61;  &2,  leucocytes  with  single,  polymorphic,  or  fragmented  nuclei,  the  latter  suf- 
fering karyolysis  and,  consequent  ly,  death  :  g,  endothelial  cell  with  nucleus  in  spirem 
stage  of  karyokinesis,  demonstrating  the  proliferation  of  those  cells. 
20 


306  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

one  point  with  the  walls  of  the  capillaries  and  reaching  out  in  Col- 
umns or  bands  among  the  cells  of  the  granulation-tissue.  Here  they 
may  become  united  writh  each  other,  forming  loops  that  spring  from 
the  same  capillary  vessel,  or  connect  it  with  other  capillaries.  Sub- 
sequently these  solid  columns  or  bands  of  cells  become  channelled, 
the  cells  forming  the  walls  of  the  new  vessels,  the  lumina  of  which 
communicate  with  those  of  the  parent  capillaries  (Fig.  271). 

FIG.  271. 


New-formation  of  bloodvessels  in  granulation-tissue.    (Birch-Hirschfeld.) 

The  granulation-tissue  thus  formed  is  continuous  with  the  adja- 
cent uninjured  fibrous  tissues,  and  serves  to  separate  the  tissues  that 
have  been  killed  or  have  undergone  irrevocable  degeneration  from 
the  living  tissues  that  lie  beneath  it.  The  dead  mass  is  finally 
loosened  and  cast  oif,  leaving  a  surface  of  growing  granulations. 
While  the  cells  in  the  superficial  portions  of  this  granulation-tissue 
continue  to  multiply  and  produce  fresh,  young,  undifferentiated  tis- 
sue, the  deeper  portions  undergo  differentiation,  the  formative  powers 
of  the  cells  being  no  longer  preoccupied  with  the  production  of  new 
cells,  but  diverted  to  the  elaboration  of  intercellular  substances  of 
a  fibrous  character  (Fig.  272). 

During  this  process  the  cells  dwindle  in  size  as  the  intercellular 
substances  accumulate  between  them,  and  may  suffer  complete  extinc- 
tion. This  may  be  due  to  atrophy  in  consequence  of  pressure  exerted 
by  the  fibrous  constituent  of  the  intercellular  substances,  which  has  a 
marked  tendency  to  shrink  as  it  becomes  older.  Another  probable 
reason  for  the  disappearance  of  many  of  the  cells  may  be  the  lack 
of  a  well-defined  lymphatic  circulation  in  the  granulation-tissue 
and  the  young  cicatrix,  which,  if  it  existed,  would  serve  to  assist 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE. 


307 


in  the  nutrition  of  the  tissue.  There  is  a  manifest  advantage  to 
the  whole  organism  in  this  absence  of  lymphatics  in  granulation- 
tissue,  for  the  absorption  of  injurious  substances  from  the  region 
beyond  the  granulations  is  hindered.  But  the  nutrition  of  the 
granulations  themselves  is  impoverished  and  the  fibrous  tissue 


FIG.  272. 


Newly  formed  fibrous  tissue  from  a  case  of  pleurisy :  a,  pulmonary  alveolus  filled  with  an 
exudate  largely  composed  of  leucocytes  (pneumonia ;  stage  of  gray  hepatization  passing 
into  resolution) ;  b,  alveolus,  from  which  the  disintegrated  exudate  has  fallen  out. 
Before  the  alterations  in  structure  due  to  inflammation  took  place  this  alveolus,  and 
the  one  above  it,  lay  immediately  beneath  the  pleura.  The  thin  pleuritic  membrane 
has  now  been  destroyed  and  its  place  taken  by  the  fibrous  tissue  of  inflammatory  pro- 
duction, which  fills  nearly  the  whole  field  of  vision,  c,  thin-walled  bloodvessel  in  that 
fibrous  tissue.  This  and  those  like  it  form  a  part  of  the  older  portion  of  the  granulation- 
tissue  which  has  replaced  the  fibrinous  exudate  at  first  covering  the  lung  (see  p.  313).  The 
granulation-tissue  between  these  vessels  has  organized  into  a  young  fibrous  tissue,  d, 
younger  granulation-tissue;  e,  recently  formed  bloodvessel  in  the  latter;/,  masses  of 
carbon  deposited  in  the  tissues  by  leucocytes,  which  have  transported  it  thither  from  the 
air-passages.  These  deposits  existed  before  the  acute  inflammation  began.  This  form 
of  pigmentation  is  called  "anthracosis." 

that  results  from  its  differentiation  is  of  comparatively  low  vital- 
ity. While  the  tissue  is  young,  succulent,  and  highly  vaseular- 
ized  by  capillaries,  this  deficiency  in  its  organization  may  not  be 
apparent ;  but  as  the  intercellular  substances  contract  they  com- 
press the  vessels  and  cause  obliteration  of  many  of  them,  with 
atrophy  and  disappearance  of  their  cellular  walls  (Fig.  273). 


308 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


When,  as  in  the  example  originally  chosen,  the  injury  affects 
tissues  that  are  normally  covered  with  epithelium,  the  cells  of  that 
tissue  proliferate  at  the  edges  of  the  granulations  until  a  layer  of 
epithelium  completely  covering  them  is  produced.  The  whole  proc- 
ess of  repair  comes  to  an  end  with  the  formation  of  a  dense  fibrous 
tissue  that  is  only  slightly  vascularized  by  thin-walled  bloodvessels 
and  is  poor  in  cells.  This  is  the  scar,  composed  of  "  cicatricial " 
tissue  (Fig.  273).  Upon  the  skin  it  is  covered  with  epithelium ; 

FIG.  273. 


Dense  fibrous  tissue,  or  cicatricial  tissue  resulting  from  pericarditis  :  a,  fibrous  tissue,  almost 
devoid  of  nuclei  and  vessels  derived  from  granulation-tissue;  6,  lumen  of  a  small 
remaining  vessel;  c,  moderate  round-cell  infiltration  in  the  deeper  portion  of  the 
fibrous  tissue,  resulting  from  an  immigration  of  leucocytes,  and,  perhaps,  also  from  a 
slight  irritative  proliferation  of  the  fixed  cells  of  the  tissue ;  d,  subpericardial  adipose 
tissue. 

but  there  are  no  papillae  beneath  this  covering,  and  the  epithelium 
is  as  poorly  nourished  as  the  cicatricial  tissue  beneath  it. 

The  cells  of  higher  function  in  the  damaged  part  which  have  not 
been  irremediably  injured  pass  through  the  changes  that  will  pres- 
ently be  described  in  the  section  on  regeneration. 

The  course  of  a  simple  acute  inflammation,  as  outlined  above, 
may  be  modified  and  complicated  by  a  number  of  circumstances 
to  such  an  extent  that  these  variations  must  be  briefly  described. 

1.  The  Healing  of  Fractures. — When  a  bone  is  broken  the  rejuv- 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE.  309 

enescence  affects  the  tissues  of  the  periosteum  and  endosteum,  as 
well  as  the  surrounding  connective  tissue  of  the  fibrous  type.  In 
the  subsequent  differentiation  of  the  granulation-tissue,  which  in 
this  case  is  called  the  "  callus/'  those  cells  which  have  been  derived 
from  the  periosteum  and  endosteum  produce  bone,  which  becomes 
continuous  with  the  osseous  tissue  of  the  fragments  and  restores  the 
continuity  of  the  broken  bone.  It  is  evident  that  in  this  case  the  re- 
juvenescence of  the  bone- form  ing  cells  has  not  caused  a  reversion  to 
an  entirely  unspecialized  type  of  connective-tissue  cell.  It  is  equally 
evident  that  in  the  production  of  cicatricial  tissue  the  cells  of  fibrous 
tissue  retain  their  special  formative  powers  after  rejuvenescence. 

2.  Suppuration. — This  is  occasioned  by  the  persistent  action  of  a 
damaging  cause  which  is  accompanied  by  the  presence  of  substances 
exerting  a  "  positive  chemotactic  influence  "  upon  leucocytes  (i.  e., 
attracts  those  cells)  and  at  the  same  time  effecting  solution  of  the 
tissue-elements.  In  clinical  experience  nearly  all  cases  of  suppu- 
ration are  due  to  infection  with  bacteria ;  but  purulent  inflamma- 
tions of  very  limited  extent  may  be  caused  experimentally  by  chem- 
ical substances  free  from  micro-organisms. 

Suppuration  does  not,  however,  always  follow  infection,  even  by 
pyogenic  bacteria.  Sometimes  the  virulence  of  the  bacteria  is  too 
slight  for  the  production  of  chemotactic  substances  in  sufficient 
quantity  to  attract  large  numbers  of  leucocytes.  Sometimes  it  is  so 
great  that  the  chemotactic  influence  becomes  "  negative  "  (i.  e.,  repels 
leucocytes),  or  the  leucocytes  are  killed  before  they  can  collect  in 
sufficient  numbers  to  form  pus.  The  relations  between  the  leuco- 
cytes and  the  chemotactic  substances  are  quantitative :  if  the  sub- 
stances be  present  in  too  great  dilution,  they  fail  to  attract  leuco- 
cytes ;  if  in  too  great  concentration,  they  repel  them.  Nor  are  bac- 
teria and  their  products  the  only  substances  that  attract  leucocytes. 
Bits  of  dead  tissue  may  do  the  same,  a  fact  which  would  promote 
their  absorption  through  the  agency  of  the  leucocytes. 

These  points  will  be  made  clearer  if  illustrated  by  an  example, 
for  which  purpose  an  infection  of  the  kidney  through  the  vascular 
system  may  be  selected.  If  a  section  be  made  through  the  organ  so 
as  to  include  a  focus  of  infection,  the  bacteria  will  be  found  in  the 
bloodvessels.  The  appearance  of  the  tissues  surrounding  the  ves- 
sel will  depend  upon  a  number  of  circumstances  ;  among  others,  the 
length  of  time  that  has  elapsed  since  the  bacteria  were  brought  to 
the  part.  In  one  case  the  walls  of  the  obliterated  vessel  and  the 


310 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


tissues  in  the  vicinity  may  show  chiefly  necrotic  changes ;  the 
tissue  will  be  diffusely  stained,  the  nuclei  either  unstained,  only 
faintly  tinged,  or  broken  into  fragments  that  take  the  dye  in  vari- 
ous intensities  (Fig.  274).  Around  this  necrosed  tissue  there 


FIG.  274. 


Secondary  infection  of  the  kidney  in  a  case  of  erysipelas.  (Faulhaber.)  a,  capillary  con- 
taining streptococci ;  b,  renal  tubule  containing  a  hyaline  cast ;  c,  renal  tubule  filled  by 
a  deposit  of  calcareous  material.  In  the  neighborhood  of  the  capillary  containing  the 
bacteria  the  tissues  have  been  necrosed,  and  have  become  reduced  to  a  granular  detritus 
through  the  peptonizing  action  of  products  formed  by  the  bacteria.  More  remotely,  at 
the  upper  left,  the  cells  in  the  renal  tubules  are  in  a  state  of  albuminoid  degeneration.  In 
this  case  the  bacteria  are  evidently  of  great  virulence  ;  probably  capable  of  destroying 
leucocytes  that  wandered  into  their  neighborhood,  through  concentration  of  the  poisons 
produced ;  for  the  section  contains  no  evidence  of  a  round-cell  infiltration  with  emigrated 
leucocytes. 

may  be  a  ring  of  leucocytes,  easily  identified  by  their  irregularly 
shaped  or  fragmented  nuclei,  which,  unless  necrosis  has  taken  place, 
are  more  deeply  stained  than  the  normal  nuclei  of  the  surrounding 
kidney.  The  central  necrosis  is  due  to  the  poisons  that  have  accom- 
panied the  bacteria  at  the  time  of  infection  or  have  been  subsequently 
produced  by  them.  Having  killed  a  portion  of  the  tissue  through 
the  action  of  these  poisons,  the  bacteria  thrive  upon  the  dead  mat- 
ter and  produce  fresh  poisons,  which  increase  the  area  of  necrotic 


STRUCTURAL   CHANGES  DUE  TO  DAMAGE. 


311 


FIG.  275. 


s#-r:r  -<*v. 


feeginning  abscess-formation  in  the  kidney.  (Faulhaber.)  The  suppurative  inflam- 
mation is  due  to  secondary  infection  by  bacilli  carried  to  the  kidney  from  a  phleg- 
monous  inflammation  of  the  neck,  a,  a,  bacilli  in  the  capsule  of  a  Malpighian  body, 
the  necrotic  glomerulus  of  which  is  seen  in  the  upper  half  of  the  figure  ;  6,  bacilli  in 
the  lumen  of  a  convoluted  tubule.  The  epithelial  lining  of  that  tubule  has  been  de- 
stroyed and  dissolved  ;  only  three  nuclei,  almost  devoid  of  chromatin,  remaining.  The 
basement-membrane  is  also  partially  destroyed,  c,  beginning  abscess-formation  in  the 
interstitial  tissue  between  the  convoluted  tubules.  These  foci  of  suppuration  are  crowded 
with  leucocytes,  in  some  of  which  the  nuclei  have  become  poor  in  chromatin  through 
the  action  of  the  poisons  present.  Among  the  leucocytes  are  a  few  bacilli,  the  virulence 
of  which  can  only  be  moderate,  since  comparatively  few  of  the  leucocytes  are  necrotic. 


FIG.  276. 


EK 


Pus  from  virulent  abscess-formation.  (Grawitz.)  The  leucocytes  show  marked  necrotic 
changes,  chromolysis.  c,  c,  well-preserved  leucocytes;  E.  K.,  connective-tissue  cells 
from  the  neighboring  granulations ;  z,  similar  cells  necrosed. 


312  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

action.  Toward  the  periphery  of  the  inflammatory  focus  these 
poisons  are  more  dilute,  and  exert  a  positive  chemotactic  influ- 
ence upon  the  leucocytes,  stimulating  their  emigration  and  prog- 
ress toward  the  centre  of  the  inflamed  area.  If  they  advance 
too  far,  however,  or  the  accumulating  poisons  become  too  con- 
centrated, they  suffer  necrosis  or  degeneration  in  the  same  manner 
as  the  tissues  of  the  part.  In  this  way  the  necrotic  process  may 
advance  more  rapidly  than  the  restricting  inflammatory  process  can 
cope  with  it.  But  to  a  certain  extent  the  poisons  they  produce  are 
injurious  to  the  bacteria  themselves,  so  that  as  they  become  more 
concentrated  the  growth  of  the  bacteria  is  checked.  The  injurious 
influence  of  the  bacteria  upon  the  tissues  is  also,  after  a  time,  miti- 
gated by  the  production  within  the  body  of  chemical  substances 
called  "  antitoxins,"  which  neutralize  the  poisons  produced  by 
the  bacteria.  Other  substances  may  also  be  produced  which 
have  a  germicidal  action.  There  will  come  a  time,  therefore,  pro- 
vided the  individual  lives,  when  the  productive  inflammatory  process 
on  the  part  of  the  tissues  will  predominate  over  the  destructive 
action  of  the  bacteria  and  confine  the  poisonous  area  within  a  zone 
of  granulation-tissue.  This  demarcation  does  not  take  place  in  most 
cases  until  a  collection  of  pus,  an  abscess,  has  been  formed  in  and 
around  the  area  of  necrosis.  The  appearances  are  then  different, 
and  require  a  brief  description. 

An  abscess  or  collection  of  pus  within  the  tissues  contains  a  fluid 
of  serous  character,  in  which  there  is  such  a  great  number  of  sus- 
pended leucocytes  that  they  give  it  a  milky  or  creamy  appearance. 
This  liquid  is  pus  (Figs.  275,  276,  and  292).  The  walls  enclosing 
the  pus  are  composed  of  granulation-tissue  infiltrated  with  emi- 
grated leucocytes  making  their  way  to  the  fluid  contents.  The 
liquefaction  of  the  tissues  which  makes  the  central  cavity  pos- 
sible is  the  result  of  maceration,  the  disintegrating  action  of  the 
leucocytes,  and,  probably  in  still  greater  degree,  is  due  to  a  pep- 
tonizing  action  exerted  by  the  bacteria  or  their  products.  There 
is  now  an  antagonistic  action  between  the  bacteria  and  their 
products  and  the  tissues,  in  which  possibly  the  phagocytic  action 
of  the  leucocytes  may  aid  the  tissues.  The  activities  of  the  tis- 
sues are  directed  to  the  formation  of  cicatricial  tissue ;  the  bac- 
teria and  their  products  tend  to  impede  those  activities  or  to 
destroy  their  results.  If  the  destructive  action  predominates,  the 
pus  increases  in  amount  and  a  burrows,"  following  the  direction  of 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE.  313 

least  resistance,  until  it  is  finally  discharged  along  with  some  of  the 
bacteria  and  poisons.  This  frequently  brings  relief,  and  the  abscess 
becomes  an  open  wound,  which  heals  by  granulations  in  the  way 
already  outlined. 

In  other  cases  the  conflict  between  the  bacteria  and  the  tissues 
may  be  more  evenly  balanced  and  the  pus  confined  by  granulations, 
which  are  injuriously  aifected  on  the  surface,  but  progress  toward 
the  formation  of  fibrous  tissue  in  their  deeper  portions.  Such 
a  lining  of  granulation-tissue  is  called  the  "  pyogenic  membrane" 
of  the  abscess.  Similar  pyogenic  membranes  are  formed  on  the 
walls  of  sinuses  resulting  from  the  discharge  of  an  abscess  when  the 
infection  is  still  sufficient  to  prevent  the  growth  of  healthy  and  vig- 
orous granulation-tissue,  or  when  the  burrowing  of  the  pus  before 
its  discharge  has  been  so  slow  that  the  granulations  surrounding 
the  sinus  have  become  organized  in  their  deeper  portions  and  are 
no  longer  capable  of  nourishing  young  and  active  tissues  at  the 
surface.  In  such  a  case  curetting  of  the  sinus-wall  would  remove 
this  imperfectly  nourished  tissue  and  promote  the  development  of 
vigorous  granulations. 

Still  another  variation  of  the  process  is  possible  when  the  infec- 
tion becomes  very  greatly  reduced  in  virulence  or  the  bacteria  die. 
In  this  case  the  granulations  grow  and  obliterate  the  cavity  in  case 
its  contents  are  absorbed,  leaving  a  puckered  scar,  or  its  contents 
may  become  inspissated  through  absorption  of  the  serum,  and  the 
leucocytes  be  converted  into  a  cheesy  mass  by  fatty  degeneration 
combined  with  necrosis ;  in  which  case  the  resulting  mass  becomes 
encapsulated  by  cicatricial  tissue.  The  resulting  nodules  are  liable 
to  subsequent  calcareous  infiltration. 

3.  Fibrinous  Inflammation. — This  frequently  affects  the  serous 
membranes,  the  lung,  etc.  A  case  of  lobar  pneumonia  may  be 
selected  as  a  typical  example. 

After  a  preliminary  congestion  of  the  vessels  in  the  walls  of  the 
pulmonary  alveoli  an  exudate,  consisting  of  serum  and  red  cor- 
puscles, with  a  comparatively  small  number  of  leucocytes,  is 
poured  out  into  the  alveoli.  Here  fibrin  is  formed,  so  that  the 
exudate  becomes  solid  (Fig.  268).  This  constitutes  the  stage  of 
"  red  hepatization."  This  stage  gradually  passes  into  that  of  "  gray 
hepatization,"  in  consequence  of  an  immigration  of  leucocytes  into 
the  fibrinous  exudate,  the  red  corpuscles  meanwhile  losing  their 
coloring-matter,  so  that  the  red  color  due  to  them  passes  into  a 


314 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


gray  (Fig.  272,  a).  In  favorable  cases  a  stage  of  "  resolution  "  fol- 
lows that  of  gray  hepatization ;  the  fibrin  disintegrates,  and  the 
exudate  becomes  softened  (Fig.  272,  6)  and  is  expectorated.  This 
is  not  the  invariable  outcome.  Sometimes  the  fibrinous  exudate  is 
replaced  by  new-formed  fibrous  tissue,  granulation -tissue,  develop- 
ing from  the  alveolar  walls,  and  the  alveoli  become  obliterated.  The 
process  in  that  case  is  similar  to  that  which  affects  the  pleura. 

The  pleural  surface  over  the  parts  of  the  lung  which  are  the  seat 
of  the  pneumonia  is  usually  also  the  seat  of  a  similar  inflammation  ; 
but  here  the  course  of  the  process  is  a  little  different.  There  are 
fewer  red  blood -corpuscles  and  less  serum  in  the  first  exudate  that 
is  formed,  probably  because  the  proximity  of  the  bloodvessels  to 
the  pleural  surface  is  less  immediate  than  the  corresponding  rela- 
tions in  the  pulmonary  tissue  (Fig.  277).  The  exudate  therefore 

FIG.  277. 

c  bed  Ic 


E 


Sfo<*3« ' 


# 


*J 


ML 


Exs 

Fibrinous  pleurisy,  ten  hours  after  its  inception.  (Abramow.)  Lg,  lung,  in  which  three 
alveoli  are  shown  in  section.  These  contain  an  exudate,  consisting  chiefly  of  red  blood- 
corpuscles  and  fibrin  in  somewhat  granular  form.  In  the  alveolar  walls  are  capillaries 
containing  either  red  corpuscles  or  leucocytes.  ML,  membrana  limitans  of  the  subendo- 
thelial  areolar  tissue ;  E,  endothelium  with  nuclear  chromolysis ;  F,  fibrin ;  Ic,  leuco- 
cytes; D,  mass  of  red  corpuscles,  fibrin,  and  leucocytes,  the  latter  with  polymorphic 
nuclei ;  a,  &,  c,  red  corpuscles  in  various  stages  of  decolorization  and  disintegration ;  D 
and  F  make  up  the  exudate  upon  the  pleural  surface;  Exs,  exudate  in  the  pulmonary 
alveoli. 

first  appears  as  a  layer  of  fibrin  upon  the  surface  of  the  pleura.  This 
may  subsequently  disintegrate  and  be  absorbed,  or  granulation-tis- 
sue may  develop  from  the  pleura  beneath  it  and  grow  into  the  fibrin, 
causing  its  gradual  absorption  and  replacement  with  fibrous  tissue. 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE. 


315 


In  this  way  a  fibrous  thickening  of  the  pleura  is  formed,  which 
remains  as  an  enduring  evidence  of  the  inflammation  that  caused  it 
(Fig.  272).  Again,  it  may  happen  that  the  inflammatory  process  is 
communicated  to  the  costal  pleura  where  it  is  in  contact  with  the 
visceral  layer.  In  this  case  fibrin  is  formed  on  both  pleural  surfaces, 
which  become  agglutinated  in  case  they  are  in  contact.  When,  in 
such  cases,  the  interposed  fibrin  is  replaced  by  cicatricial  tissue,  per- 
manent fibrous  adhesions  between  the  lung  and  thoracic  wall  result. 
When  the  exudate  contains  sufficient  serum  to  prevent  the  agglutina- 
tion of  the  two  pleural  surfaces  such  adhesions  do  not  take  place,  but 
each  pleural  surface  receives  a  permanent  layer  of  fibrous  thickening. 
Fibrinous  inflammation  may  affect  other  tissues  than  those  of  the 
serous  membranes  (Figs.  278  and  279). 

FIG.  278. 


Fibrinous  leptomeningitis :  a,  cerebral  cortex ;  b,  torn  bloodvessel  entering  the  brain  from 
the  pia  mater;  c,  fibrous  tissue  of  the  pia  mater;  d,  the  same  tissue  infiltrated  with  emi- 
grated leucocytes ;  e,  fibrinous  exudate  in  the  wide-meshed  areolar  tissue  of  the  pia 
mater. 

4.  Serous  Inflammations. — Like  the  fibrinous,  these  inflammations 
are  common  affections  of  the  serous  membranes.  Pleurisy  is  often 
an  inflammation  of  this  sort.  The  exudation  is  chiefly  serous,  of  a 
light-straw  color,  and  either  quite  clear  or  containing  flakes  of 


316 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 

FIG.  279. 


Fibrinous  leptomeningitis :  a,  cerebral  cortex  ;  ft,  serum,  with  detritus,  separating  the  brain 
from  the  pia  mater ;  c,  bloodvessel  of  the  pia  mater,  the  walls  of  which  are  infiltrated 
with  emigrating  leucocytes  ;  d,  fibrinous  exudate ;  e,  smaller  vessel  of  the  pia. 

fibrin.  Fibrin  is  also  frequently  deposited,  or  rather  formed,  upon 
the  pleural  surfaces ;  but  agglutination  of  the  opposed  surfaces, 
with  the  formation  of  adhesions,  is  prevented  by  the  fluid  that 
keeps  them  apart.  Another  common  site  for  serous  inflammations 
is  the  skin,  slight  burns  causing  a  serous  exudation  under  or  within 
the  epidermis,  the  horny  layer  of  which  is  raised  to  form  the  cover- 
ing of  a  blister.  Serous  inflammations  may  also  affect  other  por- 
tions of  the  body  (Fig.  280). 

Under  the  microscope  a  few  leucocytes  and  blood-corpuscles  can 
be  detected  in  the  serous  exudate.  Some  of  the  leucocytes  may  be 
infiltrated  with  fat-globules,  which  they  have  appropriated  from  the 
debris  of  degenerated  cells.  These  drops  of  fat  may  be  so  numer- 
ous as  to  obscure  the  nucleus  and  completely  fill  the  cytoplasm,  dis- 
tending the  cell  to  fully  twice  its  normal  size.  These  cells  have 
received  the  name  "compound  granule-cells"  (Fig.  195).  When 
the  inflammation  affects  a  serous  surface  detached  and  swollen 
endothelial  cells  may  also  be  present  in  the  fluid. 

5.  Catarrhal  inflammations  are  those  which  affect  mucous  mem- 
branes, with  the  production  of  a  fluid  exudate  appearing  upon  their 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE. 


317 


surfaces.  In  the  exudate,  besides  the  usual  constituents,  there  are 
desquamated  epithelial  cells  and  a  variable  amount  of  mucus. 
Mucus,  it  will  be  remembered,  is  a  substance  normally  secreted  upon 
the  mucous  membranes,  where  it  serves  to  protect  the  underlying 
cells.  When  those  membranes  are  irritated  the  supply  of  mucus  is 
increased.  In  catarrhal  inflammations  it  may  be  so  abundant  as  to 

FIG.  280! 


5iv 

1   V^SQA  'ij^.^'^ 


Serous  leptomeningitis :  a,  cedematons  fibrous  tissue  of  the  pia  mater,  the  fibrous  elements  of 
the  tissue  being  separated  by  the  serous  exudate ;  6,  group  of  leucocytes,  probably  held 
together  in  part  by  fibrin;  c,  granuliir  fibrin  and  detritus;  b  and  c,  and  other  similar 
masses,  lie  in  the  serum,  which  occupies  the  whole  field  between  the  visible  elements. 

predominate  over  the  elements  of  the  exudate,  so  that  the  fluid 
appearing  on  the  surface  of  the  membrane  has  a  viscid  character. 
In  other  cases  the  mixed  secretion  and  exudate  may  be  muco-serous 
or  muco-purulent  (Fig.  281). 

In  catarrhal  or  broncho-pneumonia  the  exudate  appearing  in  the 
alveoli  of  the  lung  is  of  a  serous  character,  with  an  admixture  of 
desquamated  cells  from  the  alveolar  walls  and  a  variable  number  of 
leucocytes.  These  sometimes  give  the  exudate  an  almost  purulent 
appearance. 

6.  Croupous  inflammation  is  an  inflammation  of  a  surface,  char- 


318 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


acterized  by  the  formation  upon  it  of  a  "  pseudomembrane  "  com- 
posed chiefly  of  fibrin. 

7.  Diphtheritic  inflammation  is  a  term  usually  applied  to  inflam- 
mation affecting  the  tissues  underlying  a  free  surface.  It  is  char- 
acterized by  local  death  of  the  superficial  portions  of  those  tissues 
with  an  accompanying  coagulation  (Fig.  263).  The  result  is  the 

FIG.  281. 


Tr«wfc         .       '    />;-:  ^>rT-v~r..T*V.^       -.    .        Q  - 


"  fe1lP'v\j;;S 


Catarrhal  bronchitis :  a,  areolar  tissue  of  the  submucosa,  infiltrated  with  serum  and  leuco- 
cytes ;  b,  alveolus  of  a  mucous  gland,  infiltrated  at  the  periphery  by  leucocytes.  The 
epithelium  is  undergoing  colliquative  necrosis,  and  in  the  centre  of  the  lumen  are  a  few 
leucocytes  with  fibrin,  c,  c',  bloodvessels,  c'  shows  an  infiltration  of  the  wall  by  emi- 
grating leucocytes,  d,  muscularis  mucosse ;  e,  subepithelial  areolar  tissue  of  the  mucous 
membrane,  infiltrated  with  serum  and  leucocytes  ;  /,  columnar  epithelium  of  the  surface 
in  a  state  of  colliquative  necrosis ;  g,  exudate  within  the  bronchus.  In  this  portion  of 
the  bronchus  the  destructive  processes  are  so  acute  that  the  epithelium  is  destroyed, 
instead  of  stimulated  to  the  production  of  excessive  mucus. 


formation  of  a  membranous  mass  of  dead  tissue  closely  adhering 
to  the  tissues  beneath,  a  so-called  "true  membrane/7  in  contradis- 
tinction to  the  "false  membrane"  of  croupous  inflammation.  This 
membrane  is  subsequently  separated  from  the  underlying  tissues  by 
the  formation  of  granulations,  leaving  an  ulcer. 

8.  The  "  infective  granulomata,"  such  as  tubercle,  gumma,  and  the 


STRUCTURAL   CHANGES  DUE  TO  DAMAGE. 


319 


nodules  of  leprosy  and  glanders,  are  forms  of  subacute  inflamma- 
tion which  owe  their  peculiarities  to  the  infections  that  occasion 
them.  The  tubercle,  caused  by  the  presence  of  the  tubercle  bacil- 


FIG.  282. 


-., 


ft 

Early  stage  of  experimental  tuberculosis ;  cornea  of  rabbit.  (Schieck.)  Five  days  after 
inoculation.  Rejuvenescence  and  beginning  degeneration  in  fixed  cells  of  the  fibrous 
tissue,  a,  karyolysis  in  a  cell  affected  by  a  group  of  tubercle  bacillrwithin  the  cyto- 
plasm ;  b,  karyokinetic  figure  in  another  cell. 

lus,  is  the  most  common  of  these  inflammations  and  may  be  taken 
as  a  type  of  the  whole  group. 

The  tubercle   bacillus   does   not  always  produce   the   little  in- 

FIG.  283. 


*^5    • 

*V  "-   w  -  J5S£*r*^e^ 

^r^     -.__•«•    • 


Early  stage  of  experimental  tuberculosis;  cornea  of  rabbit.  (Schieck.)  Ten  days  after  inocu- 
lation. Beginning  of  a  tubercle.  The  "  epithelioid  "  or  young  connective-tissue  cells  are 
masked  by  the  presence  of  leucocytes  with  denser  nuclei,  which  have  been  attracted  by 
the  chemotactie  (positive  chemotaxis)  influence  of  the  materials  accumulating  in  the 
inflamed  focus. 

flammatory  nodules  called  "tubercles."  It  sometimes  occasions 
a  suppurative  inflammation  of  sluggish  type,  forming  "cold  ab- 
scesses," or  purulent  inflammations  of  mucous  membranes.  It 


320  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

may  also  cause  serohsemorrhagic  exudations  from  the  serous 
membranes — e.  g.,  the  pleura;  but  the  most  characteristic  tissue- 
reaction  due  to  its  presence  is  the  formation  of  the  tubercle.  This 
is  the  result  of  a  rejuvenescence  of  the  connective-tissue  cells, 
without  any  preceding  exudation,  and  an  attempt  at  the  pro- 
duction of  granulation-tissue  around  the  bacilli  (Figs.  282  and 
283).  These  multiply  so  slowly  that  they  and  their  products  exert 
merely  an  irritation  on  the  cells  of  the  tissue,  stimulating  them 
to  reproduce,  but  they  do  not  usually  cause  the  growth  of  new 
bloodvessels,  so  that  in  the  majority  of  cases  the  granulation-tis- 
sue is  not  vascularized.  Furthermore,  as  they  increase  in  number 
the  bacteria  cause  degenerative  and  necrotic  changes  in  the  cells 
that  have  been  produced,  and,  as  their  products  increase  in 
amount,  the  cells  in  the  centre  of  the  focus  of  inflammation  are 
destroyed  (cheesy  degeneration,  p.  274),  while  those  at  the  periph- 
ery multiply,  causing  an  increase  in  the  size  of  the  inflamma- 
tory nodule  or  tubercle.  The  multiplication  of  the  cells  is  often 
hindered  to  a  certain  extent  by  the  poisons  present;  the  nuclei 
divide,  but  the  protoplasm  fails  to  undergo  a  corresponding  di- 
vision. In  this  way  multinucleated  cells,  called  "  giant-cells/7  are 
produced. 

As  the  result  of  these  processes  a  developing  tubercle  presents  the 
following  appearances  under  the  microscope.  In  the  centre  is  a 
mass  of  cheesy  matter,  composed  of  fine  granules  of  fat,  albuminoid 
material,  and  fragments  of  nuclei,  the  result  of  degenerative  and 
necrotic  changes  caused  by  the  bacterial  poisons.  Around  this 
mass  is  a  zone  of  rather  large  "  epithelioid  "  cells,  which  belong  to 
the  granulation-tissue,  and  among  which  there  may  be  a  variable 
number  of  emigrated  leucocytes,  probably  attracted  by  the  necrosed 
tissues  in  the  centre.  Also,  near  the  centre  or  in  the  granulation- 
tissue,  a  few  giant-cells  may  be  present ;  but  they  are  not  invariably 
found,  nor  is  their  presence  a  conclusive  sign  that  the  process  is 
tubercular  (Fig.  284). 

The  ultimate  outcome  of  the  process  varies  in  different  cases. 
The  inflammatory  reaction  may  overcome  the  infection,  encapsulat- 
ing the  nodule  with  a  dense  cicatricial  tissue ;  or  the  infection  may 
conquer ;  bits  of  the  cheesy  matter  containing  tubercle  bacilli  may 
then  find  entrance  into  the  lymphatic  circulation  and  be  carried  to 
the  neighboring  lymph-glands,  establishing  in  them  new  foci  of 
tubercular  inflammation,  or  tubercle  bacilli  may  get  into  the  blood- 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE. 


321 


vessels  and  carry  the  infection  to  all  parts  of  the  body,  occasioning 
general  tuberculosis. 

The  poisonous  products  of  the  tubercle  bacilli  are  absorbed  into 
the  general  system,  producing  disturbances  of  nutrition,  emaciation, 
and  fever.  Old  encapsulated  tubercular  products  are  prone  to 
calcareous  infiltration,  but,  even  after  prolonged  encapsulation, 

FIG.  284. 


-'^s"  ••/'*•'  *" .  *  '•>  ^  •„"/*•  * 
.  <?  ,*^*«'-'  *  . 


ililiary  tubercle ;  lung  of  a  horse.  (Birch-Hirschfeld  and  Johne.)  Cheesy  degeneration  has 
only  just  begun  in  the  centre  of  the  focus  of  inflammation,  where  the  nuclei  of  epithe- 
lioid  cells  and  leucocytes  are  still  visible.  At  the  periphery  of  the  tubercle  is  a  zone  of 
round-cell  or  leucocytic  infiltration.  Three  giant-cells,  with  peripheral  nuclei,  occupy 
intermediate  positions;  around  the  tubercle  are  the  infiltrated  walls  of  pulmonary 
alveoli. 

the  tubercle  bacilli  which  have  been  imprisoned  may  retain  their 
vitality,  and,  if  for  any  reason  the  poorly  nourished  capsule  suffers 
in  its  integrity,  these  old  nodules  may  become  the  source  of  fresh 
infection.  This  is  a  not  uncommon  result  of  some  acute  disease  like 
scarlet  fever,  typhoid  fever,  or  influenza,  convalescence  from  those 
diseases  being  followed  by  the  development  of  tuberculosis  spring- 
ing from  an  old  and  long-dormant  tubercular  infection. 

In  the  lungs  the  tubercles,  as  they  increase  in  size,  involve  the 
walls  of  the  alveoli  or  the  bronchi,  and  when   the  cheesy  matter 
21 


322  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

escapes  into  the  alveoli  or  bronchi  cavities  are  produced.  The  proc- 
ess rarely  remains  a  purely  tubercular  one  in  the  lungs.  The  con- 
ditions there  (exposure  to  inspired  air)  are  favorable  to  a  mixed 
infection  with  pyogenic  bacteria,  which  hastens  the  destruction  of 
the  pulmonary  tissues  inaugurated  by  the  tubercle  bacillus. 

Isolated  tubercles,  such  as  have  been  described,  are  not  infre- 
quently met  with ;  but  it  is  more  usual  to  find  a  number  of  such 
nodules  in  close  aggregation,  each  starting  from  a  distinct  focus  of 
infection.  As  these  enlarge,  their  peripheries  coalesce,  and  finally 
their  cheesy  centres  meet  and  blend.  Meanwhile  fresh  young 
nodules  are  formed  around  the  older  mass,  and  thus  the  tubercular 
disintegration  of  the  tissues  spreads.  It  is  for  this  reason  that 
tubercular  ulcers — e.  g.,  of  the  intestine — have  swollen  and  under- 
mined borders  (Fig.  285). 

FIG.  285. 


Tubercular  ulcer  of  the  intestine.  (Kaufmann.)  The  cavity  of  the  ulcer  was  formed 
through  disintegration  and  removal  of  the  cheesy  matter  formed  in  the  earlier  tuber- 
cles. Now  the  base  of  the  ulcer  is  formed  by  necrosed  and  cheesy  material,  beneath 
which  eight  or  nine  distinct  tubercles  are  distinguishable,  those  in  the  centre  extending 
into  the  muscular  coat  of  the  intestine.  The  infection  has  also  extended  into  the  lymph- 
atics beneath  the  serous  coat,  where  three  tubercles  can  be  seen. 

The  other  granulomata  have  peculiarities  due  to  their  special 
causes,  which  are  pretty  clearly  defined  in  typical  cases ;  but,  as 
in  tuberculosis,  these  inflammations  may  in  certain  instances  be 
structurally  indistinguishable  from  those  due  to  other  causes. 


Chronic  Inflammation. 

A  consideration  of  the  infective  granulomata  makes  the  fact  clear 
that  inflammation  may  occur  without  the  production  of  a  distinct 
exudate,  the  damaging  cause  merely  exciting  the  tissues  to  prolifer- 
ation ;  but  in  that  group  of  inflammations  the  excitation  of  the  tis- 
sues was  sufficiently  intense  to  occasion  the  development  of  a  tissue 
closely  resembling  the  granulations  of  acute  inflammation.  For 
this  reason  they  were  designated  as  subacute  inflammations. 

There  is  another  group  of  inflammations  in  which  the  irritation 
of  the  tissues  is  not  sufficient  to  induce  a  rejuvenescence  of  the 
cells  in  such  a  pronounced  degree  as  to  cause  their  reversion  to  a 


STRUCTURAL   GUANOES  DUE  TO  DAMAGE. 


323 


comparatively  undifferentiated  condition.  No  granulations  are, 
therefore,  produced,  but  the  cells  are  simply  stimulated  to  a  forma- 
tive activity  that  is  abnormal  to  the  part.  This  is  the  group  of 
chronic  inflammations,  of  which  three  or  four  examples  will  be 
cited. 

Chronic  periosteal  inflammation  may  be  induced  by  a  number  of 
damaging  causes  of  slight  intensity,  but  repeated  application.  The 
response  which  the  cells  of  the  periosteum  make  to  this  irritation 
is  a  revival  of  their  formative  activity  and  the  production  of  bone, 
which  forms  an  "  epiphyte,"  or  other  osseous  excrescence,  apparently 
springing  from  the  surface  of  the  older  bone.  Similar  new-forma- 
tions of  bone  may  take  their  origin  from  the  endosteum,  forming 

Fro.  286. 


Cirrhosis  of  the  liver;  chronic  interstitial  hepatitis.  (Kaufmann.)  a,  lobules  of  the  liver; 
b,  increased  interstitial  fibrous  tissue,  the  result  of  the  inflammatory  process ;  c,  collec- 
tion of  nuclei  in  the  fibrous  tissue,  showing  that  the  process  is  still  in  progress ;  d,  thick- 
ened capsule  of  the  liver. 


layers  that  encroach  upon  the  lumina  of  the  Haversian  canals  or 
the  medullary  cavity  of  the  bone.  These  deposits  are  more  diffuse 
than  those  springing  from  the  external  surface  of  the  bone,  probably 
because  they  arise  as  the  result  of  a  more  widespread  irritation,  such 
as  the  presence  of  some  noxious  substance  in  the  circulation,  and  not 
from  a  localized  point  of  irritation. 

Another  example  of  this  group  is  presented  by  cirrhosis  of  the  liver, 


324  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

selected  from  among  the  chronic  interstitial  inflammations  that  may 
affect  any  of  the  organs  of  the  body.  In  hepatic  cirrhosis  there  is  a 
redundant  production  of  fibrous  tissue  around  the  branches  of  the  por- 
tal vein,  and,  therefore,  appearing  between  the  "  lobules  "  of  the  liver 
(Fig.  286).  This  has  the  same  tendency  as  other  cicatricial  tissue  to 
contract,  and  that  contraction  causes  atrophy  of  the  hepatic  cells 
through  the  pressure  it  exerts  upon  them.  There  may  be  another  cause 
for  this  atrophy  of  the  liver-cells,  which  will  be  more  comprehensible 
after  considering  the  probable  etiology  of  the  interstitial  inflamma- 
tion itself.  This  appears  to  be  caused  by  the  absorption  of  irritating 
substances  from  the  digestive  tract,  which  are  carried  in  most  con- 
centrated form  by  the  portal  vein  to  the  liver.  Here  they  stimulate 
the  cells  of  the  connective  tissue  to  produce  fresh  fibrous  tissue 
around  the  branches  of  that  vessel.  But  it  is  quite  possible  that 
those  same  substances  may  act  injuriously  upon  the  parenchymatous 
cells  of  the  liver,  impairing  their  nutrition  and  rendering  them 
especially  liable  to  atrophy  under  the  increased  pressure  from  the 
fibrous  tissue  in  their  neighborhood. 

While  the  interstitial  inflammation  is  in  progress  the  connective 
tissue  of  Glisson's  capsule  appears  not  only  increased  in  amount, 
but  more  highly  cellular  than  normal.  This  is  due  in  part  to  a 
multiplication  of  the  fixed  cells  of  the  fibrous  tissue,  in  part  to 
a  round-cell  infiltration — i.  e.,  an  immigration  of  leucocytes.  This 
immigration  is  more  abundant  in  some  cases  than  in  others,  as  would 
be  expected,  since  the  process  must  be  subject  to  exacerbations,  due 
to  fluctuations  in  the  amount  of  the  irritating  substances  brought  to 
the  liver.  In  fact,  we  should  hardly  expect  to  find  a  sharp  division 
between  the  slowest  chronic  inflammation  and  such  inflammations 
as  approach  the  character  of  a  subacute  manifestation  of  the  same 
process. 

A  third  example  of  the  chronic  inflammatory  process  may  be 
found  in  the  reaction  of  the  tissues  around  the  necrotic  mass  result- 
ing from  bland  embolism.  Suppose  one  of  the  vessels  of  the  kidney 
to  be  plugged  by  an  aseptic  body.  The  tissues  normally  supplied  with 
blood  through  that  vessel  will  die  (Fig.  293).  But  the  presence  of 
this  dead  tissue,  although  it  contains  no  micro-organisms,  acts  as  an 
irritant  upon  the  surrounding  tissues,  which  respond  by  the  produc- 
tion of  a  capsule  of  fibrous  tissue.  The  necrosed  tissues  may 
remain  within  this  capsule,  or  they  may  be  absorbed,  in  which  case 
the  capsule  shrinks  to  a  puckering  mass  of  dense  fibrous  tissue. 


STRUCTURAL   CHANGES  DUE  TO  DAMAGE. 


325 


In  like  manner  a  n on- infectious  foreign  body  may  become  encapsu- 
lated within  any  of  the  tissues  of  the  body. 

Still  another  example  of  chronic  interstitial  inflammation  appears 
to  be  furnished  by  cases  in  which  the  parenchyma  has  suffered 
atrophy  or  some  other  form  of  destruction,  and  the  loss  is  made 
good  by  the  production  of  fibrous  tissue  without  a  precedent  forma- 
tion of  granulations.  In  embolism  of  a  branch  of  one  of  the 
coronary  arteries  supplying  the  heart-muscle  the  destruction  of  the 
muscle-fibres  seems  to  stimulate  the  formative  activities  of  the  cells 
of  the  interstitial  fibrous  tissue.  The  deduction  that  the  production 
of  fibrous  tissue  is  the  direct  result  of  a  loss  of  parenchyma  is,  how- 
ever, not  quite  clear,  for  the  stimulus  to  tissue-production  may 

FIG.  287. 


f 


Chronic  interstitial  inflammation.  Early  stage  of  productive  interstitial  neuritis.  (Nau- 
werck  and  Barth.)  The  section  is  from  the  anterior  root  of  a  lumbar  nerve.  It  repre- 
sents a  number  of  apparently  normal  medullated  nerve-fibres  in  cross-section,  with 
proliferation  of  the  cells  of  the  endoneurium,  as  is  evidenced  by  the  abundance  of  nuclei 
in  that  tissue. 

result  from  the  unusual  strain  brought  upon  the  part  of  the  heart 
which  is  deprived  of  the  usual  support  of  muscular  tissue.  It 
may  be  that  other  cases  in  which  a  loss  of  parenchyma  is  replaced 
by  fibrous  tissue  are  also  not  due  to  stimulation  of  fibrous-tissue 
production  because  of  that  loss,  but  are  to  be  explained  in  a  man- 
ner analogous  to  the  explanation  of  cirrhosis  already  offered. 

Further  examples  of  interstitial  inflammations  are  shown  in  Figs. 
287  and  288. 


326  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

From  the  examples  that  have  been  given  it  will  be  noticed  that, 
amid  all  its  protean  manifestations,  the  inflammatory  process  is  fun- 


FIG.  288.  . 
a        b'  b 
|         I    I 

L^x;i*£«Sl*«tar4l 
I* 


si 


•• 


Chronic  interstitial  myocarditis,  late  stage :  a,  dense  fibrous  tissue,  the  final  result  of  the 
interstitial  inflammation ;  6,  b',  b",  atrophied  cardiac  muscle-cells ;  b',  vacuolation  of  a 
less  atrophic  coll ;  b",  section  showing  anastomotic  branch  joining  two  cells ;  c,  partially- 
obliterated  bloodvessel. 

damentally  the  same,  but  susceptible  of  many  variations  ;  and  when 
the  conditions  are  not  too  adverse  it  leads  to  a  removal  of  the  cause 
of  an  injury  and  to  a  more  or  less  complete  repair  or  patching  of 
the  tissues  that  have  been  damaged. 

III.  INCIDENTAL   CONSEQUENCES   OF   DAMAGE   AND 
INFLAMMATION. 

The  damage  and  ensuing  inflammation  affecting  a  part  of  the 
body  not  only  occasion  changes  in  the  structure  of  that  part,  but 
also,  through  those  changes,  very  frequently  cause  morbid  conditions 
in  remote  parts.  It  will  be  impossible  to  enumerate  all  the  possi- 
bilities in  this  connection,  but  a  few  examples  will  suffice  to  show 
their  importance.  It  is  obvious  that  chronic  interstitial  hepatitis 
(Fig.  286)  must  affect  the  circulation  in  the  portal  system  of  vessels. 
The  inflammatory  fibrous  tissue  formed  between  the  lobules  of  the 
liver,  and,  therefore,  around  the  portal  vessels  within  that  organ,  pos- 
sesses the  same  tendency  to  contract  after  its  formation  that  is  mani- 
fested by  cicatricial  tissue  of  more  acute  inflammations,  though  perhaps 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE. 


327 


in  less  degree.  This  contraction  would  suffice  to  compromise  at 
least  the  smaller  branches  of  the  portal  vein  entering  the  lobules, 
so  as  to  obstruct  the  current  of  blood  flowing  through  them.  The 
result  is  an  increase  of  pressure  in  the  portal  circulation  and  the 
production  of  passive  hyperaemia  or  congestion  of  the  organs  in 
which  the  portal  radicles  are  situated. 

This  passive  congestion  results  in  a  dilatation  of  the  vessels  in 

FIG.  289. 


Brown  induration  of  the  lung,  the  result  of  chronic  passive  congestion  caused  by  valvular 
disease  of  the  heart :  a,  small  radicle  of  the  pulmonary  vein,  dilated  and  filled  with 
blood  ;  6,  alveolar  wall  in  cross-section,  thickened  and  containing  an  abnormal  number 
of  nuclei  (evidence  of  an  increase  of  tissue,  a  chronic  interstitial  pneumonia) ;  e,  surface- 
view  of  an  alveolar  wall,  showing  similar  abundance  of  nuclei  and  a  dilatation  of  the 
capillaries,  evidenced  here  and  elsewhere  in  the  section  by  a  double  row  of  corpuscles  in 
a  capillary ;  d,  cavity  of  an  alveolus ;  e,  alveolus  containing  serum,  red  corpuscles,  and 
leucocytes,  and  also  large  pigmented  cells.  These  are  chiefly  leucocytes  which  have 
taken  up  pigment  from  the  red  corpuscles  that  have  disintegrated — phagocytes.  Some 
of  these  large  cells  may  be  desquamated  epithelial  cells  from  the  alveolar  walls,  in 
a  swollen  and  degenerated  condition.  The  presence  of  serum  is  demonstrated  by  the 
fact  that  the  cells  in  the  alveolus  are  not  lying  against  the  alveolar  walls.  The  escape 
of  the  blood-corpuscles  from  the  capillaries  is  a  result  of  the  sluggish  circulation. 


those  organs  and  a  thickening  of  their  walls,  and  also  frequently 
induces  a  chronic  interstitial  inflammation.  It  may  also  so  impede 
the  lymphatic  circulation  and  impair  the  nutrition  of  the  vascular 


328  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

walls  as  to  give  rise  to  an  excessive  transudation  of  serum  and 
occasion  oedema  and  ascites. 

Similar  chronic  passive  hyperaemias  may  follow  those  inflam- 
matory lesions  in  the  valves  of  the  heart  which  cause  either 
agglutination  and  permanent  adhesions  of  the  valvular  curtains, 
stenosis ;  or  a  contraction  of  one  or  more  of  those  curtains,  so  that 
their  proper  closure  is  prevented,  incompetency.  In  either  case  the 
circulation  is  impeded  and  the  flow  of  blood  from  the  organs  behind 
the  lesion  interfered  with  (Fig.  289). 

Haemorrhage  is  another  of  the  frequent  results  of  damage.  It 
may  be  recognized  by  the  presence  of  blood  outside  of  the  vessels. 
This  blood  at  first  contains  the  red  and  white  corpuscles  in  their 
normal  proportions,  but  after  a  lapse  of  time  the  clot  which  forms 
becomes  infiltrated  with  leucocytes  as  the  expression  of  an  inflam- 
matory reaction  induced  by  the  extravasated  blood.  Subsequently 
the  blood  disintegrates,  productive  inflammation  is  induced,  and  the 
lesion  heals,  with  the  production  of  a  scar.  This  is  often  colored 
brown  or  gray,  from  the  presence  of  pigment  derived  from  the 
hemoglobin  of  the  red  blood-corpuscles.  This  pigment  may  be 
in  the  form  of  reddish-brown  rhombic  crystals,  or  granules,  of 
haematoidin ;  or  it  may  take  the  form  of  small  granules  of  haemo- 
siderin.  The  latter  substance  contains  iron,  from  which  the  former 
is  free,  and  under  the  action  of  sulphuretted  hydrogen  produced 
by  decomposition  may  give  rise  to  sulphide  of  iron,  changing  its 
brown  color  to  black,  and  the  color  of  the  pigmentation  from  a 
brown  to  some  shade  of  gray. 

Haemorrhage  may  be  among  the  direct  results  of  damage  to  the 
tissues,  or  it  may  follow  necrotic  changes  in  the  vascular  wall. 
This  is  a  not  infrequent  occurrence  in  virulent  forms  of  infection, 
and  results  in  the  formation  of  small,  punctiform  haemorrhages ; 
for  the  vessels  necrosed  are  usually  of  small  calibre  and  surrounded 
by  tissues  sufficiently  firm  to  check  the  flow  of  blood  under  the 
slight  pressure  within  those  vessels  (Fig.  290).  But  more  copious 
haemorrhages  may  occur  in  the  course  of  slowly  progressing  infec- 
tions, notably  in  pulmonary  tuberculosis.  It  will  be  remembered 
that  the  walls  of  the  larger  vessels  are  composed  of  a  dense 
fibrous  tissue  rich  in  elastic  fibres  (Fig.  97).  Such  a  tissue  resists 
the  necrosing  action  of  tuberculosis  for  a  longer  time  than  the 
more  succulent  tissues  of  the  lung.  It  therefore  occasionally  hap- 
pens that  a  cavity  may  be  formed  by  the  destruction  of  the  pul- 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE.  329 

monary  tissue,  and  that  through  this  cavity,  or  within  its  walls,  a 
pervious  vessel  of  considerable  diameter  may  take  its  course.  After 
a  while  the  wall  of  this  vessel  may  become  sufficiently  destroyed  to 
yield  before  the  pressure  of  the  blood  within  it ;  rupture  may  then 
take  place,  with  the  effusion  of  considerable  blood,  haemoptysis. 
In  many  cases,  however,  such  a  result  is  prevented  by  the  forma- 
tion of  a  clot  (thrombus)  within  the  vessel  before  erosion  of  its 
wall  has  gone  far  enough  to  threaten  rupture. 

Thrombosis. — This   term    is   applied  to  the  formation  of  fibrin 
within  the  circulatory  system  during  life.     It  may  take  place  when 

FIG.  290. 


Haemorrhage  in  the  kidney  following  general  infection.  (Tizzoni  and  Giovannini.)  The 
haemorrhage  has  taken  place  within  the  capsule  of  a  Malpighian  body  and  part  of  the 
extravasated  blood  has  passed  into  the  corresponding  uriniferous  tubule.  The  glomer- 
ulus  has  been  compressed  (to  the  right),  an  occurrence  which  probably  checked  the 
haemorrhage.  The  tissues  of  the  glomerulus  and  of  the  neighboring  tubules  are  necrotic. 

the  circulation  in  a  particular  vessel  or  in  a  portion  of  the  heart  is 
sufficiently  sluggish  to  permit  leucocytes  and,  perhaps,  blood-plates 
to  collect  and  remain  in  one  place  long  enough  for  their  disin- 
tegration to  begin.  The  elements  required  for  fibrin-formation  are 
then  set  free  and  thrombosis  results.  In  this  way  thrombi  may 
form  between  the  columnse  carnese  in  marantic  conditions,  behind 
the  curtains  of  venous  valves,  or  in  the  lumina  of  dilated  veins 
within  the  pelvis.  Thrombosis  may  also  occur  as  the  result  of  a 
roughening  of  the  intima  of  a  vessel  or  its  mechanical  destruction, 
as  in  the  tying  or  crushing  of  a  vessel. 

Thrombosis  may  be  the  result  of  disease  of  the  vessel-wall,  caused 
by  infection  or  malnutrition.  The  affection  of  the  veins  known  as 
septic  thrombophlebitis  may  be  selected  as  one  of  the  more  impor- 
tant acute  lesions  of  the  vessels.  This  is  caused  by  an  infection  of 


330 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


the  vascular  wall,  which  eventually  reaches  the  intima.  Here  a 
fibrinous  inflammation,  analogous  to  that  of  a  serous  membrane 
(p.  313),  is  induced.  The  roughness  of  the  intima  so  occasioned 
induces  the  formation  of  a  thrombus  (Fig.  291).  Meanwhile  the 


Thrombophlebitis,  incident  to  erysipelas  of  the  arm.  (Kaufmami.)  The  thrombus  occupies 
about  two-thirds  of  the  lumen  of  the  vein,  which  is  surrounded  by  areolar  tissue  infil- 
trated with  serum  and  leucocytes. 

septic  process  in  the  wall  of  the  vessel  progresses  and  extends  into 
the  thrombus,  which  is  softened.  The  rate  of  softening  may  now 
exceed  that  of  thrombus-formation,  in  which  case  the  thrombus  is 
broken  up,  and  particles  containing  some  of  the  bacteria  occasion- 
ing the  inflammation  gain  access  to  the  venous  circulation  (see 
Embolism). 

Embolism. — The  obstruction  of  a  vessel  by  a  foreign  body 
brought  from  a  distance  by  the  circulating  blood  is  called  embolism. 
The  foreign  body,  or  embolus,  is  usually  a  small  mass  of  fibrin ; 
but  it  may  be  air,  fat  (derived,  for  example,  from  the  medulla  of  a 
fractured  bone),  a  calcareous  fragment,  or  a  particle  of  tissue. 

With  the  exception  of  the  branches  of  the  portal  vein,  the  vessels 
obstructed  by  an  embolus  are  arterial.  The  results  of  embolism 
will  depend,  first,  upon  the  anatomical  distribution  of  the  vessel 
plugged,  whether  there  are  anastomotic  branches  of  considerable 
calibre  beyond  the  site  of  the  obstruction ;  second,  upon  the  nature 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE.  331 

of  the  embolus,  whether  it  contain  pathogenic  bacteria  or  not.  In 
the  former  case  the  embolus  is  called  a  septic,  in  the  latter  a  bland, 
embolus. 

In  septic  embolism  an  acute  inflammation,  similar  to  that  at  the 

FIG.  292 


*p;v 

<      -    *  :  L 


•-    *>*<$£ 
«$>'% 


>:^v.    , 


Metastatic  abscess  in  the  heart,  due  to  septic  embolism.  (Birch-Hirschfeld.)  The  abscess- 
cavity  contains  red  blood-corpuscles  and  leucocytes  with  fragmented  nuclei.  The 
muscle-fibres  within  and  near  the  cavity  have  been  killed  and  many  of  them  dissolved. 

site  of  the  original  lesion,  is  induced  by  the  bacteria  brought  with 
the  embolus.     If  the  original  inflammation  was  suppurative,  ab- 


Experimental  ansemic  infarction  of  the  kidney ;  rabbit.  (Foa.)  a,  necrotic  tissue  formerly 
supplied  by  the  artery  obstructed  ;  b,  zone  of  affected  tissue  surrounding  the  infarct.  In 
this  zone  the  renal  tubules  contain  hyaline  casts,  and  their  lining  epithelium  shows  an 
evanescent  tendency  to  proliferate,  some  of  the  cells  containing  karyokinetic  figures,  c, 
normal  renal  tissue. 

scesses,  callecf  metastatic  abscesses,  are  formed  around  each  septic 
embolus  (Fig.  292). 

In  bland  embolism,  when  there  are  ample  anastomoses  between 
the  vessel  plugged  and  other  vessels  beyond  the  site  of  the  embolus, 


332 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


no  serious  result  follows.  Thrombosis  takes  place  around  the  em- 
bolus,  but  the  circulation  beyond  it  is  maintained  through  the  anas- 
tomotic  vessels.  If,  however,  the  anastomoses  are  not  sufficient  to 
maintain  the  nutrition  of  the  tissues  normally  supplied  by  the  ob- 
structed vessel,  those  tissues  suffer  necrosis  (Fig.  293).  Such  a 
mass  of  necrosed  tissue  is  called  an  "  infarct." 

Infarcts  are  divided  into  anaemic  and  hsemorrhagic  infarcts.  The 
former  occur  when  the  tissues  are  entirely  deprived  of  blood  by 
embolism  (Fig.  293) ;  the  latter  take  place  when,  through  innutri- 
tion of  the  vessels  in  the  part  affected  by  infarction,  blood,  derived 
from  the  veins  or  through  capillary  or  other  fine  anastomoses,  is 
permitted  to  pass  into  the  interstices  of  the  necrosed  tissues. 
These  then  appear  surcharged  with  blood.  The  most  striking 
example  of  hsemorrhagic  infarction  is  that  following  bland  em- 
bolism of  a  branch  of  the  pulmonary  artery  (Fig.  294). 

FIG.  294. 


Haemorrhagic  infarct  of  the  lung.  (Kaufmann.)  The  section  contains  a  portion  of  the 
plugged  vessel  beyond  the  site  of  the  embolus.  It  and  the  pulmonary  alveoli  are  filled 
with  blood,  which,  in  the  latter,  has  passed  through  the  capillary  walls,  rendered  per- 
vious by  malnutrition.  This  blood  may  be  derived  from  the  pulmonary  vein  and  also 
from  the  bronchial  artery,  which  communicates  with  the  capillaries  of  the  alveolar  walls. 

Phagocytosis. — In  the  preceding  pages  incidental  mention  has 
been  made  of  the  ability  of  leucocytes  and  other  amoeboid  cells  to 
incorporate  within  their  cytoplasm  particles  of  foreign  matter  with 
which  they  may  come  in  contact.  Such  cells  within  the  body  are 
called  "  phagocytes  "  (devouring  cells).  It  was  at  one  time  thought 
that  these  cells  had  much  to  do  with  the  killing  and  destruction 
of  pathogenic  bacteria  and  other  organisms  that  might  gain  access 
to  the  system  ;  but  it  is  now  believed  that  such  is  not  the  case. 


STRUCTURAL   CHANGES  DUE  TO  DAMAGE. 


333 


Phagocytes  do  incorporate  bacteria ;  but  if  those  bacteria  are  viru- 
lent, the  phagocyte  either  refuses  to  take  them  within  its  cytoplasm, 
or,  after  doing  so,  suffers  degeneration  or  necrosis.  It  has  no  pecu- 
liar immunity  against  the  action  of  the  bacteria.  On  the  other 
hand,  it  has  been  shown  that  the  fluids  of  the  body  are  capable  of 
diminishing  the  virulence  of  bacteria  or  of  killing  them.  It  often 
takes  some  time  for  the  production  of  the  substances  that  have  this 
effect,  and  their  elaboration  is  frequently  too  tardy  to  check  the 
destructive  action  of  the  bacteria.  But  upon  the  surface  of  granu- 
lations, from  which  absorption  is  slow  or  does  not  take  place,  the 
effects  of  the  tissue-fluids  have  been  studied  and  an  attenuation  of 
bacteria  (decrease  in  their  virulence)  observed.  These  attenuated 

FIG.  295. 


Phagocytes  from  granulations  infected  with  virulent  anthrax  bacilli.  (Afanassieff.)  a,  thread 
of  bacilli,  partly  within  and  partly  outside  of  a  phagocyte.  Both  portions  show  a  vacu- 
olation  of  the  bacilli,  indicative  of  their  degeneration,  d,  thread  almost  entirely  incor- 
porated. Within  the  cell  the  incorporated  bacilli  lie  in  vacuoles  in  the  cytoplasm  ;  prob- 
ably digestive  vacuoles.  In  6  and  e  similar  appearances  are  presented,  c,  degenerating 
thread  of  bacilli  from  the  fluid  of  the  granulations.  Vacuolation  has  also  taken  place  in 
this  thread,  showing  that  the  fluids  of  the  granulations  have  a  destructive  influence  upon 
the  bacilli. 

bacteria  may  be  taken  up  by  phagocytes  with  impunity  and  subse- 
quently digested  within  their  cytoplasm  (Fig.  295). 

The  digestion  and  removal  of  degenerated  or  dead  materials 
appear,  then,  to  be  the  useful  rdle  played  by  phagocytes.  They 
appear  to  be  the  active  agents  in  the  absorption  of  organic  frag- 
ments, such  as  fibrin,  macerated  necrotic  tissue,  etc.,  which  may  be 
present  in  the  tissues  of  the  body  (Fig.  296). 

The  majority  of  phagocytes  are  probably  leucocytes,  identical  with 


334 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


FIG.  296. 


Phagocytes  from  aseptic  granulations.  (Nikiforoff.)  C,  phagocytes  with  pseudopodia;  E, 
without  pseudopodia ;  F,  proliferating,  the  daughter-nuclei  in  the  spirem  phase  of  karyo- 
kinesis;  A,  B,  D,  with  leucocytes,  fragments  of  tissue,  and  red  corpuscles  in  their  cyto- 
plasm. 

those  in  the  blood  and  lymph ; l  but  it  is  possible  that  young  con- 
nective-tissue cells,  which  are  believed  to  possess  the  power  of  arnos- 
boid  motion,  may  sometimes  play  the  part  of  phagocytes. 

IV.  REGENERATION  OF  THE  TISSUES. 

Frequent  reference  has  been  made  to  the  power  possessed  by 
many  cells  to  restore  or  regenerate  structures  that  have  been  dam- 
aged by  influences  causing  either  necrosis  or  degeneration.  The 
ability  to  effect  this  restoration  varies  greatly  in  the  cells  of  different 
tissues,  being,  in  general,  inversely  proportional  to  the  degree  of 
specialization  to  which  they  had  attained  at  the  time  the  damage 
took  place.  We  must,  therefore,  consider  this  process  in  the  dif- 
ferent tissues  separately,  after  taking  a  general  survey  of  the  facts 
that  apply  to  all  cases  of  regeneration. 

It  is  needless  to  say  that  a  cell  which  has  once  become  necrotic 
is  incapable  of  restoration ;  but  if  the  nucleus  be  sufficiently  pre- 
served and  enough  cytoplasm  be  left  after  degenerative  changes 
have  come  to  an  end,  both  those  cellular  constituents  may  take  up 
nourishment  and  regenerate  the  parts  destroyed.  When  whole 
masses  of  tissue  have  been  killed,  but  some  of  the  same  form  of 
tissue  retains  life  and  continuity  with  the  necrosed  portion,  the 
dead  tissue  may  be  more  or  less  completely  replaced  by  tissue 

1  The  polynuclear  neutrophile  leucocytes  are  those  which  most  frequently  act  as 
phagocytes. 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE. 


335 


of  new  formation  springing  from  the  living  portion.  If  this 
takes  place,  the  cells  of  the  latter  portion  multiply  and  reassume 
those  formative  activities  that  they  possessed  during  the  develop- 
ment of  the  tissues  in  earlier  life.  The  division  of  the  cells  al- 
ways takes  place  by  the  indirect  method,  that  of  karyokinesis.  We 
must  not,  however,  assume  that  because  the  cells  of  a  tissue  may, 
under  the  influence  of  damaging  agents,  contain  karyokinetic  figures, 
they  must  necessarily  possess  the  power  of  regenerating  lost  por- 
tions of  tissue.  More  than  mere  observation  of  those  figures  is  re- 
quired to  establish  that  fact.  Such  figures  are  occasionally  met  with 
in  the  ganglion-cells  of  the  central  nervous  system,  and  they  show 
that  the  nuclei  of  those  cells  retain,  at  least  to  a  certain  extent,  the 
power  of  division.  But  this  by  no  means  implies  that  new  ganglion- 
cells,  capable  of  full  functional  activity,  can  be  produced  by  the 
division  of  an  adult  nerve-cell,  and,  as  a  fact,  such  an  occurrence 

FIG.  297. 


a — 


FIG.  299. 


Phases  in  the  regeneration  of  the  gastric  mucous  membrane;  dog.  (Griffini  and  Vassale.) 
a,  regenerated  columnar  epithelial  cells  covering  the  base  of  the  wound ;  b,  c,  karyokinetic 
figures  indicative  of  proliferation. 

does  not  appear  to  take  place.  In  Fig.  293,  zone  6,  karyokinetic 
figures  are  seen  in  the  renal  epithelium  ;  but  it  is  doubtful  whether 
they  signify  the  beginning  formation  of  new  renal  tissue  to  replace 


336  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

that  killed  in  the  anaemic  infarct.  Such  a  replacement  does  not 
take  place  in  the  kidney,  but  a  scar  of  fibrous  tissue  is  formed 
around  or  in  place  of  the  necrosed  mass.  The  karyokinetic  figures, 
then,  simply  demonstrate  a  tendency  toward  cell-division,  and  fur- 
ther observations  are  necessary  in  order  to  determine  the  significance 
of  that  tendency. 

1.  Epithelium. — The  regenerations  of  which  epithelium  is  capable 
are  very  extensive  and  perfect.      In  some  forms  of  epithelium— 
e.  g.j  the  stratified  variety  and  that  found  in  sebaceous  glands — 
the  regenerative  process  is  a  part  of  the  functional  activity  of  the 
tissue.     After  wounds  of  the  skin  the  epithelium  forming  the  epi- 
dermis regenerates  a  new  epidermis  for  the  injured  area.     In  this 
case  the  epithelial  layer,  provided  the  wound  be  extensive,  is  rela- 
tively thin  and  of  low  vitality.     This  is  not  because  the  epithelial 
regeneration  was  imperfect,  but  because  the  nourishment  it  receives 
from  the  underlying  cicatricial  tissue  is  deficient.     There  is  in  this 
case  a  lack  of  coordinate  development  in  the  regenerations  effected 
by  the  epithelium  and  underlying  fibrous  tissues.     Remarkable  ex- 
amples of  a  more  perfect  coordination  are  exhibited  in  the  regen- 
eration of  glands  (Figs.  297,  298,  and  299),  where  the  regenerating 
epithelium  and  fibrous  tissues  appear  to  cooperate  in  the  restitution 
of  lost  glandular  structures. 

The  complicated  glandular  structure  of  the  liver  is  also  capable 
of  regeneration  when  a  portion  of  that  organ  has  been  removed 
under  aseptic  precautions  (Fig.  300).  Where,  however,  the  de- 
struction is  due  to  damage  exciting  acute  inflammation  it  is  doubt- 
ful whether  any  regeneration  is  possible,  owing  either  to  the  inju- 
rious action  upon  the  cells,  or  to  the  hindrances  interposed  by  the 
regenerating  portions  of  fibrous  tissue  in  the  neighborhood. 

2.  Endothelium. — That  endothelium  is  capable  of  regeneration  is 
shown  by  the  formation  of  young  bloodvessels  during  the  develop- 
ment of  granulation-tissue  (Figs.  270  and  271). 

3.  Fibrous  Tissue. — A  mode  of  regeneration  of  this  tissue  has  been 
described  in  the  article  on  inflammation,  and  is  illustrated  in  Figs. 
269  and  270.     This  tissue,  when  fully  developed,  differs  from  nor- 
mal fibrous  tissue  in  its  density  and  freedom  from  bloodvessels  (Fig. 
273).    The  regeneration  of  a  tendon  severed  under  aseptic  precautions 
results  in  a  much  more  perfect  restitution  of  the  normal  structures. 
Here  the  cut  ends  of  the  fibre  show  softening,  swelling,  and  final 
disintegration  of  the  intercellular  substance.     Some  of  the  cells  are 


STRUCTURAL  CHANGES  DUE  TO  DAMAGE. 
FIG.  300. 


337 


, 


Section  of  regenerating  liver,    (v.  Meister.) 

also  affected  by  a  degenerative  process ;  but  others  rejuvenate,  mul- 
FIG.  301.  FIG.  302. 


/ 

Phases  in  the  regeneration  of  a  tendon  ;  guinea-pig.    (Enderlen.) 

Fig.  301.— Two  days  after  section :  a,  swollen  intercellular  substance ;  6,  karyolysis ;  c,  d,  leu- 
cocytes; e,  karyokinesis. 

Fig.  302.— Seven  days  after  section  :  a,  nucleus  of  young  connective-tissue  cell ;  6,  karyoki- 
nesis ;  c,  intercellular  substance  of  new  formation. 

tiply,  and  eventually  produce  a  highly  cellular  tissue,  which  devel- 
ops into  tendinous  fibrous  tissue  (Figs.  301,  302,  and  303). 

22 


338 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


4.  Bone. — When  a  piece  of  bone  dies  fresh  bone  is  produced 
through  a  rejuvenescence  of  the  formative  activities  of  the  periosteum 
(or  endosteum).  While  this  new  formation  of  bone  is  in  progress 
the  dead  bone  is  removed  by  phagocytes,  which  are  usually  multi- 


FIG.  303. 


S6SS = 


Phase  in  the  regeneration  of  a  tendon ;  guinea-pig.  (Enderlen.)  Seventy  days  after  sec- 
tion. The  tendon  is  still  rather  highly  cellular,  but  its  structure  is,  in  the  main,  fully 
restored.  At  the  top  of  the  figure  is  the  cross-section  of  a  blood-vessel. 

nucleated,  and  have  received  the  name  "  osteoclasts"  (bone-breakers), 
in  contradistinction  to  the  bone-forming  cells  of  the  periosteum, 
which  are  known  as  "  osteoblasts  "  (bone-builders)  (Fig.  304). 


Ik 


0 


Regeneration  of  bone.  (Earth.)  nk,  fragments  of  necrotic  bone;  rz,  osteoclasts ;  o,  osteo- 
blasts ;  Ik,  bone  of  new  formation  :  g,  bloodvessels  ;  nk',  lamina  of  dead  bone,  (sp,  acci- 
dental crack  in  the  section.) 

5.  Cartilage. — This  tissue  is  capable  of  only  a  limited  and  imper- 
fect regeneration.     Defects  in  cartilage  are  usually  made  good  by 


STRUCTURAL   CHANGES  DUE  TO  DAMAGE. 


339 


the  development  of  fibrous  tissue,  which  may  become  modified  into 
adipose  tissue,  or  by  bone-production  if  the  damage  causes  a  re- 
juvenescence of  periosteum  or  endosteum. 

6.  Smooth  Muscular  Tissue. — Non-striated  muscle-cells  are  capa- 
ble of  multiplication,  but  in  inflammatory  conditions  the  tissue  of 
the  media  of  the  vessels  does  not  appear  to  keep  pace  with  that  of 
the  intima  in  the  production  of  new  bloodvessels.  The  latter, 
therefore,  usually  lack  a  muscular  coat  and  are  thin- walled  (Fig. 
272).  In  the  uterus  and  other  situations  smooth  muscle-cells  may 
multiply  and  occasion  a  hyperplasia  of  the  tissue.  This  appears, 
however,  to  be  in  response  to  a  functional  demand,  rather  than  one 

Fro.  305.  FIG.  306. 

r . 


FI'LT.  :'.().">.— Karyokinetic  figures  in  smooth  muscular  fibres.    (Busachi.) 

Fig.  306.— Regeneration  of  a  striated  muscle-fibre.  (Kirby.)  a,  remains  of  the  old  contractile 
substance ;  6,  rejuvenating  cytoplasmic  fragments,  with  their  nuclei ;  c,  similar  fragment 
containing  a  bit  of  old  contractile  substance  and  a  nucleus  in  karyokinesis,  d. 

of  the  results  of  damage :  a  functional  hyperplasia.  Karyokinetic 
figures  have  been  observed  in  smooth  muscle-cells  after  damage, 
but  they  do  not  lead  to  a  restoration  of  the  original  tissue,  which 
heals  with  the  formation  of  a  scar  (Fig.  305). 

7.  Striated   Muscle. — When   a    striated   muscle-fibre    undergoes 


340 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


partial  degeneration  the  cytoplasm  around  the  nuclei  that  have 
been  preserved  may  increase  in  amount,  the  nuclei  may  divide,  and 
a  multinucleated  cytoplasmic  mass  result  from  the  union  of  these 
rejuvenated  portions.  From  this  mass  new  contractile  substance 
is  then  elaborated.  This  process  results  in  regeneration  of  the 
particular  fibre.  It  is  still  a  question  whether  new  striated  muscle- 
fibres  are  produced  in  consequence  of  regenerative  processes  follow- 
ing damage.  Wounds  of  voluntary  muscles  heal  through  the 
formation  of  a  cicatrix  (Fig.  306). 

8.  Cardiac  Muscle. — Karyokinetic  figures  have  been  observed  in 
the  cells  of  the  heart-muscle,  but  they  do  not  appear  to  lead  to  re- 
generation of  that  tissue,  which  heals  with  the  production  of  scar- 
tissue  when  wounded. 

9.  The  Nervous  Tissues. — Ganglion-cells  have  not  been  observed 
to  rejuvenate  so  as  to  produce  fresh  nerve-cells ;  but  if  the  cell -proc- 
ess forming  part  of  a  nerve  is  severed  from  the  cell  without  serious 
damage  to  the  cell-body,  a  new  process  or  nerve-fibre  is  developed 

FIG.  307. 
KS  KZ  KS 


Longitudinal  section  of  a  regenerating  nerve.  (Stroebe.)  N,  nerve;  P,  perineurium,  con- 
taining more  cells  than  normally ;  KZ,  phagocytes,  containing  globules  of  myelin  from 
the  medullary  sheaths  of  degenerated  fibres;  K,  nuclei  of  proliferated  cells  of  the 
neurilemma ;  F,  young  axis-cylinders ;  KS,  points  showing  the  relations  of  the  nuclei 
and  young  nerve-fibres ;  B,  bloodvessel  in  the  perineurium. 

(Fig.  307).  The  cells  of  the  neuroglia  are,  on  the  other  hand, 
capable  of  regenerating  that  tissue.  In  this  respect  the  neuroglia 
resembles  the  interstitial  tissue  of  other  organs  than  those  of  the 
central  nervous  system,  often  increasing  in  amount  when  there  is  a 
diminution  in  the  bulk  of  the  parenchyma,  due  to  disease. 


CHAPTER  XXV. 
TUMORS. 

IT  will  promote  clearness  of  conception  if  the  term  tumor  is 
restricted  to  abnormal  masses  of  tissue  produced  without  obvious 
reason  and  performing  no  function  of  use  to  the  organism. 

In  the  introductory  chapter  an  attempt  was  made  to  show  that 
under  normal  conditions  the  parts  of  the  body  develop  in  an  orderly 
manner,  which  fits  them  for  the  performance  of  work  useful  to  the 
whole  organism,  as  well  as  for  maintaining  their  own  nutrition  and 
structure.  It  was  also  pointed  out  that  parts  of  the  body,  when 
occasion  arises,  frequently  fulfil  what  appear  to  be  their  duties  to 
the  whole  body,  even  if  their  own  nutrition  or  structure  suffers 
in  consequence.  From  these  observations  we  must  conclude  that 
throughout  the  life  of  the  individual  each  part  is  controlled  in  its 
activities  by  influences  having  direct  reference  to  the  well-being  of 
the  whole  body.  Those  influences  control  not  only  the  functional 
activities  of  the  tissues  after  the  body  has  reached  the  adult  state, 
but  also  control  or  guide  the  activities  of  the  cells  elaborating  the 
body  during  development.  The  nature  of  those  influences  and 
the  mechanism  of  their  control  are  unknown  to  us.  We  are  ignorant 
of  any  reason  why  the  tissues  of  the  body  should  develop  to  a  cer- 
tain point  and  then  have  their  nutritive  and  formative  activities 
restricted  to  a  maintenance  of  the  structures  then  existent.  We 
attribute  these  phenomena  to  the  force  of  heredity,  but  the  expla- 
nation is  incomplete,  for  that  term  merely  expresses  the  fact  that 
the  offspring  of  an  individual  develops  into  a  likeness  to  its  parent. 

In  the  development  of  tumors  these  guiding  or  controlling  influ- 
ences are  in  abeyance,  sometimes  in  greater,  sometimes  in  less  de- 
gree. The  tissues  do  not  grow  to  meet  a  functional  demand  imposed 
upon  them  by  the  needs  of  the  body,  as  appears  to  be  invariably  the 
case  in  the  increase  of  tissue  during  the  development  of  the  indi- 
vidual. Instances  of  growth  bringing  about  such  adaptation  to 
altered  demands  occur  after  the  body  has  attained  full  development, 

341 


342  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

but  they  are  characterized  as  functional  hyperplasia  or  hypertrophy, 
not  as  tumor-formation,  and  are  arrested  when  the  needs  giving  rise 
to  them  are  met.  This  limitation  of  growth  does  not  hold  in  the 
case  of  tumors. 

Our  knowledge  of  the  normal  forces  guiding  and  restricting  the 
development  of  the  tissues  being  so  deficient,  how  can  we  expect  to 
understand  the  causes  underlying  the  development  of  tumors  ?  The 
marvel  is  not  that  certain  cells  should  occasionally  continue  to  mul- 
tiply and  exercise  their  formative  powers  without  reference  to  the 
needs  of  the  whole  body.  The  fact  that  such  occurrences  are  so 
rare  awaits  explanation.  Familiarity  with  what  is  usual  is  apt  to 
blind  us  to  the  fact  that  it  is  not  explained,  and  when  our  atten- 
tion is  directed  to  what  is  unusual  we  ask  an  explanation  of  the  ex- 
ception. A  knowledge  of  the  etiology  of  tumors  appears  to  await 
the  acquisition  of  a  deeper  insight  into  the  nature  of  hereditary 
transmission  and  of  the  conditions  which  that  transmission  ordi- 
narily imposes  upon  the  tissues  throughout  the  life  of  the  individual. 

Tumors  arise  from  the  cells  of  pre-existent  tissues.  The  fact  that 
those  cells  in  producing  a  tumor  form  a  tissue  which  is  functionally 
useless  is  evidence  that  the  usual  guiding  influences  mentioned 
above  no  longer  completely  control  their  activities.  The  degree 
in  which  that  control  is  lost  is,  however,  by  no  means  the  same  in 
all  cases  of  tumor-production.  Sometimes  the  tissues  of  the  tumor 
attain  nearly  if  not  quite  the  complete  structural  differentiation  pos- 
sessed by  the  tissue  in  which  it  found  origin.  In  such  cases  only 
that  degree  of  normal  control  which  has  reference  to  function 
appears  to  be  abolished,  the  cells  retaining  their  special  formative 
activities  in  nearly  full  measure  and  producing  a  tissue  resembling 
the  parent  tissue.  Such  tumors  may  be  regarded  as  an  expression 
of  only  a  moderate  relaxation  of  the  influences  normally  controlling 
growth.  They  are  clinically  benign. 

While  such  tumors  closely  simulating  normal  tissues  are  of  occa- 
sional occurrence,  in  the  majority  of  tumors  the  formative  powers 
of  the  cells  from  which  they  develop  display  certain  departures  from 
the  normal  types  of  the  classes  to  which  they  belong,  and  the  structure 
of  the  tumor  becomes  different  from  that  of  the  tissue  in  which  it 
arose.  This  departure  from  the  normal  formative  activity  is  usually 
a  reversion  to  a  more  primitive  type  of  tissue-formation,  the  control- 
ling influences  normally  guiding  the  cells  being  weakened  to  such  a 
degree  that  the  tissues  produced  fail  to  acquire  the  structural  differ- 


TUMORS.  343 

entiation  of  the  parent-tissue.  This  failure  in  structural  differen- 
tiation may  be  so  great  that  the  resulting  tumor  resembles  embryonic 
tissue.  Such  tumors  are  clinically  malignant,  and,  in  general,  it  may 
be  said  that  the  degree  of  malignancy  is  approximately  proportional 
to  the  lack  of  specialization  exhibited  by  the  formative  activities  of 
the  cells.  Up  to  this  point  we  have  considered  two  possibilities  in 
the  production  of  tumors  :  1 .  The  production  of  a  tumor  by  cells 
which  no  longer  respond  to  the  needs  of  the  organism  in  perform- 
ing work  for  the  general  good,  but  which  remain  subject  to  the 
influences  controlling  the  structural  differentiation  of  the  parent- 
tissue.  2.  The  formation  of  a  tumor  by  cells  which  are  less  re- 
strained by  normal  influences  and  which  exercise  their  formative 
powers  without  conforming  to  the  special  differentiation  exhibited 
in  the  parent-tissue.  This  we  may  regard  as  a  reversion  of  the 
cells  to  a  less  specialized  state,  in  which  they  exercise  their  forma- 
tive powers  in  elaborating  tissues  corresponding  to  those  normally 
present  at  some  earlier  stage  in  the  development  of  the  individual. 

There  is  a  third  possibility.  The  reversion  just  described  may  be 
conceived  as  affecting  the  cells  involved  in  tumor-production,  but 
those  cells,  instead  of  forming  a  tissue  corresponding  to  the  degree 
of  reversion  they  have  suffered,  may  become  specialized  along  some 
divergent  line  of  development  and  produce  a  tissue  more  or  less 
akin  to  that  of  the  parent-tissue.  Thus  a  tumor  composed  of  bone 
may  be  produced  within  some  other  form  of  connective  tissue,  such 
as  cartilage  or  fibrous  tissue.  The  dissimilarity  between  the  tis- 
sues of  a  tumor  and  those  of  the  part  in  which  it  grows  would  seem, 
from  this  point  of  view,  to  depend  upon  the  degree  of  reversion 
that  had  taken  place.  Even  after  a  tumor  has  once  been  formed, 
portions  of  it  may  acquire  a  different  structure,  due  to  reversion  on 
the  part  of  some  of  its  cells  or  a  modification  of  their  formative 
activities.  There  appears  to  be  a  limit  to  the  extent  of  these  rever- 
sions. It  is  found  in  the  early  differentiation  of  the  three  embry- 
onic layers.  Cells  derived  from  the  mesoderm,  for  example,  do  not 
seem  to  revert  to  such  an  undifferentiated  condition  that  they  can 
develop  tissues  like  those  normally  springing  from  the  epiderm  or 
hypoderm. 

A  still  further  complexity  of  structure  may  arise  from  the 
formative  tendencies  of  different  cells  within  the  same  growth 
developing  along  different  lines  of  specialization.  This  occasions 
the  production  of  "mixed"  tumors,  composed  of  various  tissues 


344  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

arranged  in  a  manner  usually  quite  unlike  that  of  any  normal 
organ. 

In  consequence  of  the  numerous  variations  in  tissue-production 
which  may  participate  in  their  development  it  follows  that  tumors 
have  a  marked  individuality,  and  that  only  certain  types  of  more 
frequent  occurrence  can  be  described.  Departures  from  those  types 
will  be  met  with  in  practice,  and  they  must  each  be  interpreted  in 
accordance  with  the  insight  which  the  observer  can  gain  as  to  their 
nature  and  tendencies.  The  more  atypical  the  structure  of  a  growth 
— i.  e.j  the  more  it  departs  from  the  structure  of  normal  adult  tissue 
— the  less  likely  is  it  to  prove  benign  ;  the  more  highly  cellular  it  is, 
the  more  likely  it  is  either  to  grow  rapidly  or  to  act  injuriously  upon 
the  whole  organism  :  for  its  cells  derive  their  nourishment  from  the 
general  system  and  throw  upon  it  the  task  of  eliminating  their  waste- 
products. 

Tumors  are  subject  to  morbid  changes  comparable  with  those 
affecting  normal  tissues.  They  may  be  the  seat  of  inflamma- 
tion, infiltrations,  and  degenerations.  In  fact,  the  more  cellular 
forms  are  exceedingly  prone  to  degenerative  changes,  due  probably 
to  a  relative  insufficiency  of  nourishment  consequent  upon  their 
rapid  growth  and  active  metabolism.  It  is  quite  likely  that  the 
products  of  those  degenerations,  when  absorbed  into  the  system, 
act  injuriously  upon  the  general  health. 

The  effects  upon  the  nutrition  of  the  body  occasioned  by  the 
presence  of  a  tumor  constitute  that  part  of  the  clinical  picture 
which  is  known  as  "  cachexia,"  and  is  most  marked  when  the  tumor 
is  malignant  But  cachexia  is  not  necessarily  a  sign  of  malignancy, 
and  is  not  always  present,  even  when  the  patient  has  a  very  malig- 
nant form  of  tumor.  The  degree  of  malignancy  is  measured  by  the 
rapidity  of  growth,  the  tendency  to  infiltrate  surrounding  tissues,  and 
the  liability  to  metastasis,  and  these  depend  upon  the  reproductive 
activity  of  the  cells  and  the  extent  to  which  their  formative  activity 
is  displayed  in  the  elaboration  of  firm  intercellular  substances. 
Metastasis  takes  place  when  cells  become  detached  from  a  tumor 
and  are  conveyed  to  some  other  part  of  the  body,  wrhere  they  find 
conditions  favorable  for  their  continued  multiplication.  They  then 
produce  secondary  tumors,  which  usually  closely  resemble  the  pri- 
mary growth  to  which  they  owe  their  parent-cells. 

It  is  evident  that  a  microscopical  study  of  a  tumor  may  be 
made  the  basis  of  pretty  accurate  estimates  of  its  nature  and  ten- 


TUMORS.  345 

dencies.  The  general  character  of  the  tissue  composing  it  can  be 
determined ;  an  approximate  idea  of  the  reproductive  activity  of 
the  cells  formed ;  the  tendency  to  invade  or  infiltrate  the  sur- 
rounding tissues,  and  therefore  the  probability  of  the  occurrence  of 
metastases,  estimated ;  and  the  presence  of  degenerative  or  other 
changes  observed.  The  knowledge  so  gained  will  throw  light  upon 
the  clinical  significance  of  the  tumor.  It  is  evident,  however,  that 
all  the  knowledge  required  cannot,  in  every  case,  be  learned  from 
the  examination  of  a  single  piece  of  the  tumor.  Some  of  the  neces- 
sary facts  are  best  observed  at  the  periphery  of  the  growth,  others 
in  the  central  portions,  and  in  mixed  tumors  the  various  parts  of  the 
growth  may  possess  quite  different  characters.  Every  tumor  must 
be  made  the  object  of  a  special  study,  if  all  the  information  it  is 
capable  of  yielding  is  to  be  acquired. 

Before  passing  to  a  description  of  the  more  common  types  of 
tumors  we  must  turn  our  attention  for  a  moment  to  their  classifica- 
tion and  nomenclature. 

Tumors  are  sometimes  grouped  in  two  great  divisions :  1,  the 
"  malignant  tumors,"  which  threaten  life  because  of  the  rapidity  of 
their  growth,  their  infiltration  of  surrounding  structures,  and  their 
liability  to  metastasis  ;  and,  2,  "benign  tumors,"  which  are  essentially 
harmless  unless  they  develop  in  a  situation  where  they  interfere  with 
the  function  of  some  vital  organ,  or  unless  they  appropriate  so  much 
of  the  nutritive  material  of  the  body  that  the  general  health  suffers. 
This  classification  is  a  purely  clinical  one,  and  deserves  mention  only 
because  of  its  medical  importance.  There  are  many  degrees  of 
malignancy,  and  these  can  be  estimated  in  individual  cases  only 
with  the  aid  of  deductions  from  the  structural  peculiarities  of  the 
particular  growths.  A  classification  based  upon  the  structure  of 
tumors  is,  therefore,  of  greater  value  than  one  based  merely  upon 
their  clinical  aspects,  for  it  includes  that  and  much  more  besides. 

If  we  bear  in  mind  the  fact  that  any  form  of  cell  capable  of 
multiplying  may  give  rise  to  a  tumor,  it  will  become  evident 
that  those  tumors  composed  of  a  single  variety  of  tissue  may 
be  classified  in  a  manner  similar  to  that  in  which  the  normal 
tissues  are  classified.  Such  tumors  are  grouped  under  the  term 
"histioid,"  to  distinguish  them  from  tumors  of  more  complex  struct- 
ure not  analogous  to  simple  elementary  tissues,  which  are  collec- 
tively referred  to  as  "  organoid."  The  histioid  tumors  are  desig- 
nated by  names  formed  from  the  word  indicating  the  normal 


346  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

tissue  they  most  closely  resemble  and  the  suffix  "  oma."  Thus, 
a  fibroma  is  a  tumor  consisting  essentially  of  fibrous  tissue — i.  e., 
connective-tissue  cells  with  a  fibrous  intercellular  substance — even 
if  the  arrangement  of  the  tissue-elements  is  not  quite  like  that 
of  normal  fibrous  tissue.  A  myoma  is  a  tumor  composed  of  mus- 
cular tissue,  with  only  so  much  admixture  of  fibrous  tissue  as  would 
be  comparable  with  that  found  in  masses  of  normal  muscle.  But 
as  there  -are  smooth  and  striated  muscular  tissues,  so  there  are 
leiomyomata  and  rhabdomyomata.  When  a  tumor  contains  two 
varieties  of  elementary  tissue  in  such  proportions  that  neither  can 
be  considered  as  subsidiary  to  the  other,  it  receives  a  compound 
name,  in  which  the  most  prominent  or  important  constituent  tis- 
sue is  placed  last,  being  qualified  by  the  name  of  the  less  impor- 
tant tissue.  Thus  there  are  myofibromata,  in  which  the  fibrous  tissue 
is  more  prominent  than  the  muscular  tissue ;  and  fibromyomata,  in 
which  the  muscular  tissue  predominates.  In  like  manner  three  or 
more  tissues  may  be  designated  as  forming  a  tumor  by  such  names 
as  osteochondrofibroma,  myxochondrofibroma,  etc.,  implying  that 
the  growths  are  composed  of  fibrous  tissue  with  an  admixture  of 
cartilage  and  bone,  or  cartilage  and  mucous  tissue,  etc. 

The  problem  of  classification  is  not  so  simple  when  we  take  up 
the  consideration  of  tumors  less  closely  resembling  the  normal 
tissues  that  are  found  in  the  adult  body.  Those  tumors  which  are 
akin  to  embryonic  tissues  still  retain  names  that  have  come  down 
from  earlier  times,  and  which  were  conferred  on  them  because 
of  some  characteristic  visible  to  the  unaided  eye.  Those  of  con- 
nective-tissue origin  are  called  sarcomata  (singular,  sarcoma),  which 
means  tumors  of  fleshy  nature  ;  and  those  containing  tissues  derived 
from  epithelium  are  called  carcinomata,  or  cancers,  because  by 
virtue  of  their  infiltration  of  the  surrounding  tissues  they  possess 
a  fanciful  resemblance  to  a  crab.  The  terms  sarcoma  and  carcinoma 
have,  in  the  course  of  time,  become  more  defined,  and  are  now  re- 
stricted to  certain  well-marked  types  of  structure.  The  carcinomata 
are  composed  of  fibrous  tissue  and  epithelium,  the  one  derived  orig- 
inally from  the  mesoderm,  the  other  from  either  the  epiderm  or  hypo- 
derm.  In  this  dual  origin  they  resemble  the  viscera  of  the  body, 
and  may,  therefore,  be  regarded  as  among  the  simpler  members  of 
the  group  of  organoid  tumors.  The  most  complex  members  of  that 
group  are  the  "  teratomata,"  which  contain  structures  simulating 
hair,  teeth,  bones,  etc.,  arranged  without  definite  order,  and  often 


TUMORS. 


347 


present  in  great  numbers.  They  spring  from  the  reproductive 
organs  of  the  body,  and  appear  to  be  erratic  attempts  at  the  pro- 
duction of  new  individuals. 

A  new  formation  of  bloodvessels  accompanies  the  development 
of  tumors,  and  these  vessels  are  associated  with  a  supporting  con- 
nective tissue  which  may  be  conceived  as  a  part  of  this  addition  to 
the  vascular  system  of  the  body,  rather  than  as  an  integral  part 
of  the  tumor  itself.  This  development  of  new  bloodvessels  is 
analogous  to  that  which  takes  place  in  the  course  of  some  of  the 
inflammatory  processes,  and  appears  to  be  brought  about  in  the 
same  manner. 


I.  THE   CONNECTIVE-TISSUE   TUMORS. 

1.  Fibroma. — The  structure  of  a  fibroma  is  apt  to  resemble  that  of 
the  particular  fibrous  tissue  in  which  it  develops.  Very  soft  varieties 
frequently  spring  from  the  submucous  tissues  of  the  nose,  pharynx, 


FIG.  308. 


Section  of  a  nodular  fibroma.  (Birch-Hirschfeld.)  The  dense  fibrous  tissue  is  in  irregular 
nodules,  between  which  are  bands  of  less  dense  fibrous  tissue  containing  blood- 
vessels. 

and  rectum,  forming  polypoid  growths  projecting  from  the  surface 
of  the  mucous  membrane.  They  are  composed  of  delicate  bands 
of  fibres,  loosely  disposed  to  form  an  open  meshwork,  which  is  filled 


348  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

with  a  fluid  resembling  serum.  In  the  fluid  occasional  fibres  of 
still  more  delicate  structure  may  be  seen,  together  with  lymphoid 
cells,  either  isolated  or  in  little  groups  like  imperfectly  formed 
lymph-follicles.  The  surface  of  the  growth  is  formed  by  a  layer 
of  rather  denser  fibrous  tissue,  which  is  covered  by  a  continuation 
of  the  epithelium  belonging  to  the  mucous  membrane.  Similar  soft 
fibromata  sometimes  take  origin  from  the  subcutaneous  tissues,  but 
fibromata  of  the  skin  are  usually  of  denser  structure,  the  bands 
of  fibrous  tissue  being  coarser,  more  compact,  and  less  loosely 
arranged.  CEdema  may  make  these  tumors  look  very  much  like 
the  first  variety. 

Harder  varieties  of  fibroma  take  origin  from  such  dense  forms 
of  fibrous  tissue  as  compose  the  dura  mater,  the  fasciae,  periosteum, 

FIG.  309. 


Dense  form  of  fibroma.  (Ribbert.)  Section  from  a  fibroma  of  the  dura  mater.  The  inter- 
cellular substance  is  very  compact  and  the  cells  compressed.  The  latter  are  most 
numerous  in  the  neighborhood  of  the  narrow  vessel,  a,  which,  together  with  a  branch, 
is  cut  longitudinally. 

FIG.  310. 


Jf-     ^WJ»k    V    ^ 


Dense  form  of  fibroma.  (Ribbert.)  Section  from  older  portion  of  a  keloid.  Dense  masses 
of  compact,  apparently  homogeneous  intercellular  substance  interlace  to  form  the  chief 
bulk  of  the  tissue.  The  cells  are  so  few  in  number  and  so  compressed  that  they  are 
hardly  distinguishable,  and  have  been  omitted  from  the  figure. 

etc.,  and  those  fibromata  that  occur  in  the  uterus  are  of  similar 
character.     They  are  usually  composed  of  nodular  masses  of  dense 


TUMORS. 


349 


structure,  which  are  held  together  by  a  more  areolar  fibrous  tissue 
supporting  the  larger  bloodvessels  of  the  tumor  (Fig.  308).  Among 
the  hardest  of  the  fibrous  new-formations  is  the  keloid,  which  in 
its  oldest  parts  resembles  old  cicatricial  tissue,  the  fibrous  inter- 
cellular substance  being  compacted  into  dense,  almost  homogeneous 
masses  and  bands,  in  which  the  nuclei  of  the  cells  are  barely  dis- 
cernible (Figs.  309  and  310). 

Fibromata  do  not  always  have  a  nodular  character,  even  when 
they  are  of  dense  structure.     They  sometimes  occur  in  a  diffuse 

FIG.  311. 


Intralobular  fibroma  of  the  breast.  (Ziegler.)  a,  acini  and  ducts  of  the  gland;  6,  new- 
formed  fibrous  tissue;  c,  areolar  tissue  of  the  interstitium,  containing  the  vascular 
supply. 

form,  surrounding  and  enclosing  the  structures  of  the  organ  in 
which  they  develop.  Such  diffuse  fibromata  of  the  mammary  gland 
are  not  uncommon,  and  two  varieties  may  be  distinguished  :  1,  those 
in  which  the  fibrous  tissue  develops  between  the  lobules  of  the 
gland,  separating  them  from  each  other  by  broad  bands  of  dense 
character,  the  interlobular  form ;  and,  2,  the  mtralobular  form,  in 
which  the  individual  acini  of  the  gland  are  separated  and  sur- 
rounded by  bands  of  fibrous  tissue  (Fig.  31 1).  These  diffuse  fibrom- 


350  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

ata  of  the  breast  must  not  be  mistaken  for  carcinomata,  which 
they  superficially  resemble  when  the  glandular  epithelium  has 
undergone  atrophy  due  to  pressure.  In  general  appearance  under 
the  microscope  these  fibromata  resemble  the  outcome  of  a  chronic 
interstitial  inflammation,  but  they  do  not  seem  to  owe  their  origin 
to  an  inflammatory  process. 

Fibromata  may  undergo  localized  softening,  due  to  fatty  meta- 
morphosis and  necrosis.  More  frequently  they  are  the  seat  of  cal- 
cification, the  lime-salts  being  deposited  in  granules  within  the 
intercellular  substance,  or  in  little  globular  masses,  variously  aggre- 
gated. These  calcified  portions  are  apt  to  acquire  a  diffuse  blue 
color  in  sections  that  have  been  stained  with  hsemotoxylm. 

Mixed  tumors,  containing  fibrous  tissue  and  some  other  variety 
of  connective  tissue,  or  smooth  muscular  tissue,  are  common. 
Fibrosarcomata  and  fibromyxomata  are  liable  to  metastasis ;  the 
other  mixed  tumors  and  pure  fibromata  are  among  the  most  benign 
of  the  tumors. 

2.  Lipoma. — Tumors  composed  of  adipose  tissue  arise  from  pre- 
existent  fat,  or  from  fibrous  tissue  of  the  areolar  variety.     Their 
structure  very  closely  simulates  and  is  frequently  indistinguishable 
from  that  of  normal  fat  (Fig.  312).     But  they  reveal  their  inde- 
pendence of  the  general  economy  by  not   being  reduced   in  size 
during  emaciation  of  the  individual.     They  sometimes  enter  into 
the  composition  of  mixed  tumors,  such  as  lipomyxomata,  lipofibrom- 
ata,  and  fibrolipomata.     They  often  grow  to  considerable  size,  may 
be  multiple,  but  are  not  liable  to  metastasis  and  are  benign. 

Calcification,  necrosis,  and  gangrene  may  occur  in  lipornata,  but 
are  usually  confined  to  those  of  large  size. 

3.  Chondroma. — The   cartilage    entering   into   the   formation    of 
chondromata  is  usually  of  the  hyaline  variety,  but  sometimes  fibro- 
cartilages  are   also    present,  and   may,  in    rare   instances   entirely 
replace  the  hyaline  form.     The  structure  of  the  cartilages  differs 
somewhat  from  that  of  the  normal  types.     The  cells  are  less  uniform 
in  character  and  in  size,  are  more  irregularly  distributed  through 
the  matrix,  and  are  frequently  embedded  in  the  latter  without  an 
intervening  capsule.     The  tumor  is  rarely  composed  exclusively  of 
cartilage,  but  is  usually  nodular,  the  cartilaginous  masses  being  sur- 
rounded by  a  fibrous  tissue  in  which  the  vascular  supply  of  the 
growth  is  situated. 

Chondromata  generally  arise  from  pre-existent  cartilage,  bone,  or 


TUMORS. 
FIG.  312. 


351 


Lipoma  of  the  kidney.  (Birch-Hirschfeld.)  The  boundary  between  the  adipose  tissue  of 
the  tumor  and  the  renal  tissue  is  not  sharply  defined.  The  former  occupies  the  middle 
of  the  section  and  extends  to  its  lower  edge. 

fibrous  tissue.     When  they  apparently  spring  from  bone  their  true 
origin  may  be  from  small  remnants  of  cartilage  which  have  escaped 

the  normal  ossification. 

FIG.  313. 


m 


i 


Chondrosarcoma  of  the  rib.  (Ilansemann.)  The  lower  portion  of  the  section  is  exclusively 
sarcomatous.  The  upper  part  contains  cartilaginous  tissue,  but  there  are  a  few  spindle- 
shaped  cells  in  the  matrix  similar  to  those  in  the  sarcomatous  portion  of  the  growth. 

Cartilage  is  a  not  infrequent  constituent  of  mixed  tumors,  espe- 
cially of  the  parotid  gland  or  testis,  when  it  is  usually  associated 


352 


HISTOLOGY   OF  THE  MORBID  PROCESSES. 


with  mucous  and  fibrous  tissue,  adenomatous  new  formations,  or 
sarcoma  (Fig.  313). 

Chondromata  are  subject  to  a  number  of  secondary  changes,  the 
most  important  of  which  are  :  calcification  ;  conversion  into  a  spe- 
cies of  mucoid  tissue  through  softening  of  the  matrix  and  modi- 
fication of  the  cells,  which  assume  a  stellate  form ;  transformation 
into  an  osteoid  tissue,  resembling  bone  devoid  of  earthy  salts ;  or 
into  a  fairly  well-developed  calcified  bone  (Fig.  314).  Local  soften- 

FIG.  314. 


Osteoid  endochondroma.  Section  from  a  metatastic  nodule  in  the  lung.  The  cartilage  is 
atypical,  and  is  arranged  in  a  manner  simulating  that  of  cancellated  bone.  Between  the 
bands  and  lamina  of  cartilage  is  a  mixture  of  mucous  and  sarcomatous  tissue,  myxosar- 
coma,  which  has  rendered  the  tumor  subject  to  metastasis.  The  whole  tumor  may,  then, 
be  called  a  chondromyxosarcoma. 

ing  of  the  tumor  may  also  take  place  through  a  liquefaction  of  the 
matrix  and  disintegration  of  the  cells.  The  latter  may  also  undergo 
a  fatty  degeneration  in  parts  of  a  tumor  which  show  no  signs  of 
softening  of  the  matrix. 

Chondromata  are  classed  with  the  benign  tumors,  but  occasional 
instances  of  metastasis  are  on  record.  It  is  difficult  to  understand 
how  this  could  take  place  in  the  case  of  the  harder  chondromata,  in 
which  the  cartilage  is  surrounded  by  a  somewhat  dense  fibrous  tissue 
resembling  the  normal  perichondrium.  Where  there  is  an  admixt- 
ure with  either  sarcomatous  or  myxomatous  tissues,  these  confer 
a  malignant  character  upon  the  mixed  tumor,  and  it  is  quite  possi- 


TUMORS. 


353 


ble  for  fragments  of  cartilage  to  become  detached  from  the  primary 
growth  and  appear  in  the  secondary  tumors,  should  metastasis 
occur. 

4.  Osteoma. — The  most  important  tumors  containing  bone  are 
mixed  tumors  that  are  significant  chiefly  because  of  their  other 
constituents.  Small  growths  consisting  of  bone  alone,  either  in  its 
compact  or  its  spongy  form,  occur  in  the  lung,  walls  of  the  air- 
passages,  and,  rarely,  in  other  situations  (Fig.  315).  Where  bony 

FIG.  315. 


Developing  osteoma  of  the  arachnoid.    (Zanda.)    A,  dura  mater;  B,  as  yet  non-calcified 
osteoid  tissue ;  G,  bloodvessel. 

new  formations  spring  from  pre-existent  bone — e.  g.,  from  parts  of 
the  skeleton — they  are  usually  the  result  of  some  inflammatory  proc- 
ess, and  are  not  to  be  grouped  among  the  tumors. 

In  mixed  tumors  bone  is  frequently  associated  with  fibrous  tissue, 
myxoma,  sarcoma,  and  chondroma. 

The  structure  of  the  bone  in  tumors  presents  slight  departures 
from  the  normal  type,  just  as  that  of  cartilage  in  chondromata  is 
somewhat  atypical.  The  lacunae  are  apt  to  vary  in  size,  shape,  and 
distribution  more  than  in  normal  bone,  and  the  system  of  canaliculi 
is  less  perfectly  developed. 

5.  Myxoma. — The  mucous  tissue  of  myxomata  has  its  normal 
prototype  in  the  Whartonian  jelly  of  the  umbilical  cord.  In  its 
purest  form  it  consists  of  stellate  or  spindle-shaped  cells,  with  long 
fibrous  processes  that  lie  in  a  clear,  soft,  gelatinous,  intercellular  sub- 

23 


354 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


stance  containing  mucin  in  variable  quantities  (Fig.  316).  This  tissue 
is  closely  allied  to  the  other  forms  of  connective  tissues  and  tumors 
are  rarely  composed  of  mucous  tissue  alone.  There  is  usually  an 
admixture  with  fibrous  tissue,  bone,  cartilage,  fat,  or  sarcoma ;  form- 


FIG.  316. 


|r 

.  #«  _ 

Section  from  a  subcutaneous  myxoma.    (Birch-Hirschfeld.) 

ing  fibromyxoma,  osteomyxoma,  chondromyxoma,  lipomyxoma,  or 
myxosarcoma  (Fig.  317).  The  flat  endothelial  cells  of  connective 
tissue  also  sometimes  proliferate  to  such  an  extent  as  to  form  an 

FIG.  317. 


Myxosarcoma  of  the  femur.  To  the  left  of  the  section  the  tissue  is  nearly  pure  mucous 
tissue.  Toward  the  right,  this  tissue  gradually  merges  into  a  more  highly  cellular  struct- 
ure, constituting  the  sarcomatous  element  in  the  growth.  It  is  this  admixture  with 
sarcoma  that  gives  the  tumor  a  malignant  character. 

appreciable  constituent  of  the  tumor,  the  cells  being  large,  rather 
rich  in  protoplasm  and  frequently  multinucleated.  When  this  de- 
velopment is  pronounced  the  tumor  may  be  designated  a  myxen- 
dothelioma,  and  approaches  the  myxosarcomata  in  character. 


TUMORS.  355 

Mucous  tissue  is  best  studied  in  the  fresh  condition  by  pressing 
small  bits  flat  between  a  cover-glass  and  slide.  The  processes  of 
the  cells  may  then  be  seen  in  their  continuity ;  while,  if  sections 
are  prepared  after  hardening,  many  of  those  processes  will  be  cut 
in  such  a  way  that  their  connections  with  the  cells  in  the  contiguous 
sections  are  destroyed,  and  they  appear  as  fibres  lying  free  in  the 
intercellular  substance. 

Mucous  tissue  must  be  carefully  distinguished  from  cedematous 
fibrous  tissue.  Such  oedematous  tissue  possesses  cells  of  a  spindle 
or  flat  shape,  like  those  usually  met  with  in  fibrous  tissue ;  but 
the  usual  fibrous  intercellular  substance  has  a  loosened  texture, 
due  to  the  presence  of  fluid  between  the  fibres,  which  gives  the 
tissue  a  soft,  transparent  character  not  unlike  that  of  mucous  tissue. 
It  must  also  be  borne  in  mind  that  fibrous  and  adipose  tissues  are 
liable  to  undergo  a  mucous  degeneration  in  which  the  cells  assume 
a  more  stellate  form  than  is  usual  with  those  tissues,  and  the  inter- 
cellular substances  lose  their  fibrous  character  and  become  more 
homogeneous.  Such  degenerations  are  distinguished  with  difficulty 
from  the  tissue  which  originally  develops  as  mucous  tissue,  but 
they  have  nothing  in  common  with  tumors. 

Myxomata  usually  develop  in  fibrous  tissue,  adipose  tissue,  or  the 
medulla  of  bone.  In  association  with  cartilage  they  are  not  un- 
common in  the  parotid  gland.  When  pure  they  are  benign,  but 
their  association  with  sarcoma  often  gives  them  a  malignant  char- 
acter, the  degree  of  malignancy  depending  upon  that  of  the  sar- 
comatous  tissue  present. 

6.  Endothelioma. — Theendotheliomata  are  connective-tissue  tumors 
which  owe  their  origin  to  a  proliferation  of  the  flat  endothelial  cells 
that  line  the  serous  cavities,  line  or  form  the  walls  of  the  blood- 
vessels and  lymphatics,  and  are  present  in  some  of  the  lymph  and 
other  spaces  of  the  fibrous  tissues.  Young  cells  of  this  variety  do 
not  have  the  membranous  bodies  that  characterize  the  fully  devel- 
oped older  cells,  but  closely  resemble  the  cells  of  epithelium.  It 
follows  that  in  this  class  of  tumors  it  is  not  always  easy  to 
determine  the  origin  of  the  cells  from  a  mere  inspection  of 
their  shapes  and  sizes.  The  situation  and  general  structure  of 
the  tumor  will  often  decide  this  point.  Epithelial  tumors  spring 
from  pre-existent  epithelium,  either  in  some  normal  site  or  in  an 
unusual  situation  because  of  some  anomaly  of  development  (e.  <?., 
in  the  neck,  owing  to  imperfect  obliteration  of  the  branchial  clefts). 


356 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


Endotheliomata,  on  the  other  hand,  spring  from  the  connective  tis- 
sues, often  at  a  point  remote  from  any  epithelial  structures ;  e.  g.9 
the  dura  mater. 

When  the  endothelioma  owes  its  origin  to  a  proliferation  of  the 
flat  cells  lining  the  lymph-spaces  or  vessels  it  has  a  plexiform  struct- 
ure, the  young  cells  occupying  pre-existent  interstices  in  the  tissues 
or  following  the  arrangement  of  the  vessels  (Figs.  318  and  319). 
As  the  cells  grow  older  they  may  become  flattened,  and  are  then 


•-,-;   "  S»      •••:••  •:<•.-. •;-.--,.;; ,V« 

M     i  W 


Endothelioma  from  the  floor  of  the  mouth.  (Earth.)  Older  portion  of  the  growth.  This 
has  a  general  alveolar  structure,  the  alveoli  being  separated  by  a  vascularized  areolar 
tissue,  n,  n,  necrosed  groups  of  endothelial  cells ;  h,  h,  similar  necrosed  masses  that  have 
undergone  hyaline  degeneration. 

often  imbricated,  forming  little,  pearl-like  bodies.  These  may 
subsequently  undergo  degenerative  changes,  such  as  hyaline  degen- 
eration, which  convert  them  into  homogeneous  masses  or  bands. 
Where  this  takes  place  the  tumor  has  received  the  name,  "  cylin- 
droma."  Or  the  degenerated  cells  may  be  the  seat  of  calcareous  infil- 
tration. This  is  the  origin  of  the  psammomata  or  "  sand-tumors  "  of 
the  cerebral  membranes  (Fig.  320).  In  other  cases  the  cells  may 
not  acquire  the  membranous  character  of  adult  endotheliurn,  but 
continue  to  multiply  without  such  specialization.  Then  the  tumor 
partakes  of  the  sarcomatous  nature  of  the  other  connective-tissue 
tumors  of  highly  cellular  structure  and  devoid  of  any  marked 


TUMORS. 


FIG.  319. 


357 


Endothelioma  from  the  floor  of  the  mouth.  (Earth.)  Section  showing  the  advance  of  the 
growth  into  the  lymph-spaces :  a,  karyokinetic  figure  in  an  endothelial  cell.  Other  less 
well-preserved  figures  are  seen  in  other  portions  of  the  section. 

intercellular  substance.     This  is  more  particularly  the  case  when 
the  endothelial  cells  in  the   adventitia  of  the  bloodvessels  mul- 

FIG.  320. 


Early  stages  in  the  formation  of  a  psamuioma.  (Ernst.)  a,  collection  of  endothelial  cells; 
b,  similar  group  showing  imbrication  of  the  cells  and  beginning  hyaline  degeneration ;  c, 
hyaline  mass  containing  a  slight  deposit  of  infiltrated  calcareous  matter,  appearing  as 
granules. 

tiply  to  form  the  growth.     The  cells  of  the  growth  are  then  in 
intimate  relation  with  the  walls  of  the  vessels,  and  the  tumor  is 


358  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

designated  as  an  angiosarcoma  or  alveolar  sarcoma,  according  as  the 
cells  show  a  grouping  around  the  vessels  or  form  collections  occu- 
pying the  meshes  between  them  (Figs.  321,  322,  and  323). 

This  brief  outline  of  a  complicated  group  of  tumors  will  serve 
to  show  that  some  members  of  that  group  closely  simulate  epi- 
theliomata  in  their  structure,  though  they  are  quite  different  in  their 

FIG.  321. 


Endothelioma  of  the  ulna.  (Driessen.)  a,  a,  alveoli  lined  with  endothelial  cells  and  occupied 
by  blood;  6,  areolar  tissue  between  the  alveoli,  containing  capillary  vessels,  c;  d,  large 
vessel  closely  surrounded  by  proliferated  endothelium.  The  structure  of  this  tumor  is 
difficult  of  interpretation.  It  appears  most  probable  that  its  origin  lay  in  the  prolifera- 
tion of  the  endothelium  of  lymphatics,  and  that  the  blood  in  a,  a  is  due  to  commumca- 
.tions  established  between  the  bloodvessels  and  elongated  and  anastomosing  alveoli  of 
the  tumor.  The  cells  of  this  growth  contained  glycogen  (see  Fig.  249). 

origin  ;  while  other  members  of  the  group  are  essentially  sarcomata, 
owing  their  origin  to  a  particular  variety  of  connective-tissue  cells 
and  having  peculiarities  of  structure  due  to  the  situations  in  which 
those  cells  normally  occur.  The  significance  of  the  tumor  will 
depend  in  each  case  upon  its  tendency  to  grow  rapidly  and  to  infil- 
trate the  surrounding  tissues,  and  its  liability  to  metastasis.  These 
qualities  must  be  estimated  by  a  consideration  of  the  history  of 


TUMORS. 


359 


the  case  and  the  structure  and  evidences  of  proliferation  presented 

by  the  tumor  itself. 

FIG.  322. 


Angiosarcoma  of  bone.  (Kaufmann.)  The  lumina  of  bloodvessels  are  seen  in  longitudinal 
and  in  cross-section.  They  are  surrounded  by  a  highly  cellular  tissue,  derived  from  the 
proliferation  of  the  endothelium  forming  the  perivascular  lymphatics.  Such  tumors  are 
also  called  "  peritheliomata." 

7.  Sarcoma. — This  term  includes  a  variety  of  tumors  differing  in 
the  details  of  their  structure  and  in  their  clinical  significance,  but 

FIG.  323. 


Endothelioma  of  the  thyroid.  (Limacher.)  In  this  example  the  endothelial  cells  of  the 
tumor  spring  from  the  endothelium  of  the  capillary  bloodvessels.  Various  stages  in  the 
proliferation  of  that  tissue  are  represented  in  the  section. 

having  in  common   a   general    resemblance  to  imperfectly  devel- 
oped or  embryonic  connective  tissue.     Such  tissues  are  not  infre- 


360  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

quently  associated  with  other  neoplasmic  tissues  of  higher  differen- 
tiation, forming  mixed  tumors;  but  in  such  cases  the  tissues  of 
higher  type  are  not  the  result  of  a  progressive  development  on 
the  part  of  the  sarcomatous  tissue,  for  the  essential  feature  of  the 
latter  is  that  it  remains  in  a  primitive  condition,  the  formative 
powers  of  its  cells  being  chiefly  confined  to  a  reproduction  of 
fresh  cells,  and  not  to  the  elaboration  of  intercellular  substances 
which  would  convert  the  tissue  into  some  variety  of  adult 
connective  tissue.  In  this  respect,  as  well  as  in  the  absence  of 
any  natural  limitation  'of  growth,  the  sarcomata  differ  from  the 
tissues  of  somewhat  similar  structure  which  result  from  the  rejuv- 
enescence of  connective  tissue  in  the  productive  stages  of  inflam- 
mation leading  to  repair.  Some  forms  of  sarcoma  closely  resemble 
granulation-tissue,  for  both  have  the  same  origin  from  the  cells  of 
the  connective  tissues ;  but  the  two  must  be  sharply  distinguished 
from  each  other,  for  their  tendencies  and  usefulness  are  extremely 
different.  The  formation  of  granulation-tissue  has  a  definite  cause, 
and  it  undergoes  a  progressive  differentiation  into  a  dense  fibrous 
tissue,  which  terminates  the  process  (with  the  possible,  but  notable, 
exception  of  the  development  of  keloid ;  which  is,  however,  not 
sarcoma).  Sarcoma,  on  the  other  hand,  arises  without  a  well- 
defined  cause,  shows  no  tendency  to  higher  differentiation,  and 
continues  to  grow  without  any  assignable  limitations.  A  further 
difference  that  may  aid  in  the  decision  of  whether  an  undifferen- 
tiated  tissue  of  connective-tissue  type  is  sarcoma  or  due  to  inflam- 
matory processes  lies  in  the  fact  that  sarcoma  has  a  tendency  to 
infiltrate  the  surrounding  tissues,  while  the  young  connective  tissue 
that  results  from  an  inflammatory  rejuvenescence  has  not. 

Sarcomata  need  not  necessarily  have  the  structure  of  the  least 
differentiated  forms  of  connective  tissue.  Their  cells  may  show 
a  greater  differentiation  than  is  found  in  that  tissue,  and  there 
may  be  a  certain  amount  of  intercellular  substance  of  a  fibrous 
or  other  nature  separating  the  cells.  The  presence  of  such  a 
fibrous  intercellular  substance  is  an  evidence  that  the  forma- 
tive activity  of  the  cells  is  not  wholly  concentrated  in  the  produc- 
tion of  new  cells,  but  is  partly  diverted  to  the  formation  of  inter- 
cellular material.  It  is  therefore  a  sign  of  less  active  growth  than 
would  be  the  case  were  there  no  such  diversity  of  activity.  The 
intercellular  substances  also  tend  to  confine  the  cells  to  the  growth 
itself,  impeding  their  penetration  into  the  interstices  of  the  sur- 


TUMORS.  361 

rounding  tissues  (infiltration)  and  reducing  the  probability  that  some 
of  the  cells  will  be  carried  to  distant  parts  by  the  currents  of  the 
fluids  circulating  in  the  tissues  (metastasis).  It  follows  that  the 
presence  of  intercellular  substances  having  these  effects  must  re- 
duce the  degree  of  malignancy  of  the  whole  growth  if  they  are 
present  throughout  its  substance.  This  argument  is  borne  out  by 
the  results  of  experience.  The  sarcomata  might  be  arranged  in  a 
series  according  to  their  degrees  of  malignancy,  beginning  with 
those  that  are  most  malignant,  and  have  little  intercellular  substance, 
and  cells  which  are  only  slightly,  if  at  all,  differentiated,  and  end- 
ing with  those  that  can  hardly  be  considered  malignant,  and  which 
have  such  an  abundant  fibrous  intercellular  substance  that  their 
structure  closely  agrees  with  that  of  fibroma.  In  fact,  no  sharp 
line  between  these  sarcomata  and  the  fibromata  can  be  drawn.  The 
two  classes  of  tumor  merge  into  one  another :  they  have  the  same 
origin,  and  differ  only  in  the  behavior  of  their  cells  in  the  exercise 
of  their  formative  activities.  Those  differences  are,  however,  of  the 
utmost  clinical  importance. 

The  sarcomata  are  classified,  according  to  the  characters  of 
their  component  cells,  into  the  round-cell,  spindle-cell,  giant- 
cell,  melanotic,  etc.,  varieties.  They  are  also  subdivided  ac- 
cording to  the  way  in  which  those  cells  are  arranged.  The 
alveolar  sarcomata,  for  example,  consist  of  groups  of  cells  en- 
closed in  the  meshes  of  a  fibrous  network.  These  names  are, 
however,  more  descriptive  than  indicative  of  essentially  distinct 
kinds  of  tumor,  and  the  demarcation  between  the  different  varie- 
eties  is  not  a  sharp  one.  Many  sarcomata  consist  of  cells  of 
various  shapes,  either  in  different  parts  or  intermingled  throughout 
the  growth.  This  necessitates  the  insertion  of  mixed  varieties  be- 
tween the  above  groups  of  distinct  and  relatively  pure  types.  Fur- 
thermore, the  cells  not  only  differ  in  shape,  but  also  in  size,  so  that 
a  distinction  may  be  made  between  the  small  round-cell  sarcom- 
ata and  the  large  round-cell  variety ;  but  notwithstanding  the 
fact  that  this  grouping  is  somewhat  artificial,  it  has  a  certain  clinical 
value,  because  it  indicates  in  a  rough  way  the  degree  of  differ- 
entiation attained  by  the  tumor,  and  for  this  reason  it  will  be  well 
to  adhere  to  this  classification  and  to  consider  the  purer  types  sepa- 
rately, bearing  in  mind  that  the  mixed  forms  of  sarcoma  possess 
characters  intermediate  between  those  of  the  simpler  forms  upon 
which  the  classification  is  primarily  based. 


362 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


a.  SMALL  ROUND-CELL  SARCOMA. — This  variety  presents  the 
least  degree  of  structural  differentiation.  The  substance  of  the  tumor 
is  composed  of  small,  round  cells  with  single  vesicular  nuclei  enclosed 
in  very  little  cytoplasm.  They  are  so  closely  aggregated  that 
they  appear  to  be  in  contact;  but  careful  examination  will  often 

reveal  a  small  amount  of  a  nearly 
homogeneous,  finely  granular,  or 
slightly  fibrillated  intercellular 
substance  (Figs.  324  and  325). 
The  tumor  is  supplied  with  blood- 
vessels having  very  thin  walls, 

FIG.  325. 


FIG.  324. 


Small  round-cell  sarcoma  of  the  neck. 

Fig.  324.— Section  only  moderately  magnified,  showing-  the  extremely  cellular  character  of 
the  growth ;  the  great  friability  of  the  tissue  is  owing  to  the  minimal  amount  of  inter- 
cellular substance  it  contains  and  the  intimate  relations  between  the  tissue  of  the  tumor 
and  the  walls  of  relatively  large,  thin-walled  bloodvessels. 

Fig.  325.— Sketch  of  a  fragment  of  the  tumor,  more  highly  magnified.  The  cytoplasm  around 
the  nuclei  is  hardly  distinguishable,  and  the  cells  are  separated  by  only  a  small  amount 
of  an  indefinite  intercellular  substance. 

formed  of  a  single  layer  of  cells,  which  are  usually  more  protoplasmic 
than  those  of  fully  developed  endothelium.  These  vessels  may  be 
very  abundant,  but,  especially  if  the  tumor  has  been  removed  by 
operation,  they  are  likely  to  be  empty  and  their  walls  so  collapsed 
that  they  are  not  easy  of  recognition.  When  seen  in  longitudinal  sec- 
tion these  emptied  vessels  appear  as  a  double  line  of  elongated,  some- 
what fusiform  cells,  lying  in  close  contact  with  the  cells  of  the  rest 
of  the  tumor.  In  cross-section  they  are  still  more  difficult  of  detec- 
tion, since  the  swollen  endothelial  cells  then  look  very  much  like 
the  contiguous  cells  of  the  growth  itself. 

Where  the  sarcoma  is  infiltrating  the  surrounding  tissues  groups 
of  the  round  cells,  distinguished  from  the  leucocytes  which  may  be 
present  by  the  character  of  their  nuclei,  appear  in  the  interstices  of 
the  tissue,  the  formed  elements  of  which  undergo  atrophy,  either 
because  subjected  to  increased  pressure  or  because  their  nutrition 
is  interfered  with  (Fig.  326).  In  this  way  the  tumor  increases  the 


TUMORS.  363 

territory  which  it  occupies,  but  the  more  central  portions  also  grow. 
After  a  certain  stage  of  growth  has  been  attained  the  older  portion- 
of  the  tumor  are  liable  to  undergo  degenerations  or  necrosis. 

It  is  evident,  from  the  structure  of  this  variety  of  sarcoma,  that 
it  must  be  very  prone  to  suffer  metastasis.  This  may  take  place 
through  the  lymphatics  of  the  surrounding  tissues,  favored  by  the 
infiltrating  qualities  of  the  growth ;  or  it  may  take  place  through 
the  bloodvessels,  some  of  the  cells  finding  their  way  through  the 
thin  walls  of  the  vessels  in  the  tumor  itself,  or  into  the  lumina 
of  larger  vessels  through  an  infiltration  of  their  walls.  In  either 

FIG.  326. 


Small  round-cell  sarcoma  of  the  pelvis,  infiltrating  dense  fibrous  tissue. 

of  these  ways  a  generalization  of  the  growth  may  take  place,  sec- 
ondary nodules  appearing  in  many  parts  of  the  body. 

Round-cell  sarcomata  of  this  type  are  liable  to  arise  in  the 
connective  fibrous  tissue  between  the  muscles,  in  the  fasciae,  etc. 
They  also  find  their  origin  in  the  skin,  testis,  and  ovary.  They 
arc  among  the  most  malignant  of  the  sarcomata,  growing  rapidly, 
infiltrating  their  surroundings,  and  undergoing  metastasis. 

b.  LYMPHOSARCOMA. — This  variety  of  sarcoma  differs  only 
slightly  in  structure  from  the  small  round-cell  form  in  possessing 
a  somewhat  more  elaborate  stroma,  a  term  which  could  hardly  be 
applied  to  the  small  amount  of  intercellular  substance  found  in  the 
latter.  In  the  lymphosarcomata  the  cells  closely  resemble  those  of  the 
small  round-cell  variety  of  sarcoma,  but  they  lie  loosely  aggregated 
in  the  meshes  of  a  reticulum  of  fibres,  many  of  which  constitute  the 
processes  of  stellate  cells  penetrating  the  substance  of  the  growth 


364  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

and  possibly  joining  each  other  This  reticulum  is  somewhat  more 
pronounced  around  the  bloodvessels  which  it  supports.  The  cells 
may  be  shaken  out  of  this  reticulum,  if  unembedded  sections  are  agi- 
tated with  water  (Fig.  327). 

FIG.  327. 
I 


II 


Sections  from  lymphosarcomata.  (Kaufmann.)  I,  firmer  variety,  with  a  pronounced 
stroma;  from  a  mediastinal  tumor.  II,  softer  variety,  with  a  more  delicate  stroma; 
from  a  tumor  of  the  small  intestine,  a,  capillary  bloodvessel. 

This  structure  closely  resembles  that  of  the  lymphadenoid  tissue 
found  in  the  normal  lymph-nodes,  and  there  is  danger  of  con- 
founding the  growth  with  a  simple  or  inflammatory  hyperplasia  of 
those  organs.  This  danger  is  enhanced  by  the  fact  that  these  sar- 
comata frequently  find  their  origin  in  a  lymph-gland  or  the  lymph- 
adenoid  tissue  in  the  mucous  membranes.  When  the  enlargement 
of  the  gland  is  the  result  of  hyperplasia  the  superabundant  tissue 
is  confined  within  the  capsule  of  the  gland,  which  enlarges  as  its 
contents  increase  in  amount.  There  is  also  a  history  of  some 
inflammatory  process  within  the  lymphatic  province  to  which  the 
gland  belongs.  Such  is  not  the  case  when  the  increase  of  tissue  is 
due  to  the  development  of  a  tumor.  The  growth  usually  pierces 
the  capsule  of  the  gland,  and  cannot  be  traced  to  inflammatory 
causes.  This  penetration  of  the  capsule  is  an  evidence  of  the  in- 
filtrating power  of  the  growth.  Like  the  small  round-cell  sar- 
coma, this  variety  is  liable  to  early  and  extensive  metastases,  and 
is  hardly  less  malignant  than  that  form. 

c.  LARGE  ROUND-CELL  SARCOMA. — As  the  title  implies,  this 
tumor  is  composed  of  larger  cells  than  those  found  in  the  small 
round-cell  sarcomata.  The  greater  size  is  due  to  a  larger  amount 
of  cytoplasm,  in  which  are  rather  large  round  or  oval  vesicular 
nuclei,  usually  one  in  each  cell,  but  not  infrequently  cells  with  two 


TUMORS.  365 

or  even  more  nuclei  are  observed.  The  intercellular  substance  is 
more  abundant  and  more  distinctly  nbrillated  than  is  the  case  in 
the  small  round-cell  sarcomata,  but  it  is  not  uniformly  distributed 
between  the  individual  cells.  These  are  usually  aggregated  in 
groups,  which  are  surrounded  by  the  denser  bands  of  fibrous  tissue. 
From  these,  little  fibrous  twigs  may  sometimes  be  seen  penetrating 
between  the  individual  cells  of  the  group.  This  arrangement  gives 
sections  of  the  growth  an  alveolar  appearance  (Fig.  328).  The 


Large  round-cell  sarcoma  of  the  tongue :  a,  large  round  cell  containing  three  nuclei ;  6, 
delicate  fibrous  stroma  supporting  the  cells  of  the  growth.  At  the  point  b  this  stroma 
contains  a  collapsed  capillary  bloodvessel.  The  large  round  cells  are  probably  of  endo- 
thelial  origin.  The  growth  occurred  in  a  man  aged  sixty-one  years,  and  in  the  course  of 
eight  months  had  attained  the  size  of  a  hickory-nut. 

fibrous  tissue  itself  may  be  highly  developed,  resembling  the  adult 
form  ;  or  it  may  be  more  highly  cellular  and  contain  large  spindle- 
shaped  cells.  When  this  is  the  case  the  tumor  becomes  a  mixed- 
cell  sarcoma  composed  of  large  cells,  partly  round,  partly  fusiform. 

The  large  round-cell  sarcomata  spring  from  the  same  tissues 
that  give  rise  to  the  small  round-cell  sarcomata,  but  it  is  probable 
that  they  owe  their  production  in  large  measure  to  a  proliferation 
of  the  endothelial  cells  of  those  tissues,  and  are,  therefore,  etiologi- 
cally  related  to  the  endotheliomata.  They  grow  less  rapidly  than 
the  small  round-cell  and  lympho-sarcomata,  and,  as  would  be  ex- 
pected from  a  study  of  their  structure,  they  are  less  prone  to 
infiltrate  their  surroundings  or  to  be  subject  to  metastasis.  They 
are,  to  a  corresponding  degree,  less  malignant  in  their  clinical  mani- 
festations. 

d.  SPINDLE-CELL  SARCOMATA. — The  shape  of  the  cells  of  this 
group  of  tumors  betokens  a  higher  state  of  differentiation  than  is 
found  in  the  small  round-cell  sarcomata,  the  cells  having  more 


366 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


nearly  approached  the  character  of  those  found  in  the  adult  fibrous 
tissues ;  but  although  in  this  respect  all  the  tumors  of  this  group 
are  more  nearly  like  the  normal  tissues,  they  differ  greatly  among 
themselves  in  regard  to  the  extent  to  which  the  formative  activities 
of  their  cells  are  displayed  in  the  production  of  intercellular  sub- 
stances. Some  possess  hardly  more  intercellular  substance  than  the 
small  round-cell  varieties,  while  others  have  the  appearance  of  a 
rather  highly  cellular  fibrous  tissue,  the  intercellular  substances 
being  abundant. 

The  fusiform  cells  of  the  tumor  possess  oval  vesicular  nuclei, 
around  which  is  an  amount  of  cytoplasm  varying  in  the  different 
individual  growths.  Sometimes  the  cytoplasm  is  abundant,  and 
the  tumor  appears  composed  of  large  spindle-shaped  cells,  tapering 
at  their  ends  to  form  processes  of  various  lengths  (Fig.  329).  In 

FTG.  329. 


Large  spindle-cell  sarcoma.    (Birch-Hirschfeld.) 

other  cases  the  cells  are  small  and  the  cytoplasm  is  reduced  to  a 
thin  investment  of  the  nucleus,  at  the  ends  of  which  it  rapidly 
dwindles  to  a  very  thin  fibrous  process.  The  spindle-cell  sarcomata 
may,  therefore,  be  divided  into  large-  and  small-cell  varieties. 

The  cells  are  usually  arranged  with  their  long  axes  parallel  to 
each  other,  forming  bundles  or  broad  bands  of  tissue,  in  which  the 
cells  all  have  the  same  general  position.  This  direction  is  generally 
the  same  as  that  taken  by  the  bloodvessels  (Fig.  330).  These  have 
very  thin  walls,  as  in  the  preceding  varieties  of  sarcoma,  and  the 
cells  of  the  tumor  appear  to  be  in  direct  contact  with  the  outside 


TUMORS.  367 

of  the  vessels.  The  cellular  bundles  may  not  all  lie  parallel  to 
each  other,  but  frequently  are  interwoven,  so  that  a  given  section 
will  contain  longitudinal,  cross,  and  oblique  sections  of  the  indi- 
vidual cells.  Such  appearances  must  not  be  mistaken  for  the  some- 
what similar  aspect  of  sections  of  mixed-cell  sarcomata. 

The  spindle-cell  sarcomata  are  among  the  most  common  of  tu- 
mors. They  may  arise  from  any  of  the  connective  tissues.  When 
they  spring  from  the  periosteum  they  are  apt  to  have  an  imper- 
fectly formed  bony  tissue  associated  with  the  structure  of  the  sar- 

FIG.  330. 


Spindle-cell  sarcoma.  (Riudfleisch.)  Where  the  cells  of  the  tumor  lie  parallel  to  the 
plane  of  the  section  their  spindle  shape  is  manifest ;  where  they  are  perpendicular  to 
the  plane  of  the  section  their  cross-sections  appear  round.  The  bloodvessels  appear  to 
have  no  proper  walls,  but  to  be  bounded  by  the  tissue  of  the  neoplasm. 

coma.  They  then  form  osteosarcomata  or  osteoid  sarcomata,  accord- 
ing to  the  perfection  with  which  the  structure  of  normal  bone  is 
reproduced. 

In  judging  of  the  probable  malignancy  of  a  given  specimen  of 
spindle-cell  sarcoma,  the  rapidity  of  its  growth,  as  evidenced  by 
the  number  of  mitotic  figures  seen  in  the  cells,  and  the  abundance 
of  fibrous  intercellular  substance,  must  be  taken  into  consideration. 
As  a  group,  the  spindle-cell  sarcomata  are  less  malignant  than 
the  small  round-cell  sarcomata ;  but  this  is  because  the  majority 
of  spindle-cell  sarcomata  have  a  well-marked  intercellular  sub- 
stance of  fibrous  character.  Those  forms  which  are  almost  desti- 
tute of  this  are  hardly  less  malignant  than  the  small  round-cell 
variety  (Figs.  331  and  332). 

e.  GIANT-CELL,  SARCOMA. — This  form  of  sarcoma  is  charac- 
terized by  the  presence  of  large,  multinucleated  cells  lying  among 
the  other  cells  of  the  growth.  These  giant-cells  may  be  scattered 


368  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

FIG.  331. 


Example  of  a  highly  malignant  variety  of  spindle-cell  sarcoma.  Sarcoma  of  the  uterus  with 
oval  nuclei,  indicating  somewhat  spindle-shaped  cells.  In  other  respects  the  character 
of  the  tumor  resembles  that  of  a  small  round-cell  sarcoma,  a,  contiguous  fibrous  tissue 
of  the  uterus ;  b,  sarcomatous  tissue ;  c,  bloodvessels,  (v.  Kahlden.) 

FIG.  332. 


S.S.Z: 


Example  of  a  highly  malignant  spindle-cell  sarcoma.  Spindle-cell  sarcoma  infiltrating  the 
liver.  I  z,  liver-cells ;  s  s  z,  spindle-cells  of  the  sarcoma ;  c,  endothelium  of  the  intra- 
lobular  capillaries.  (Heukelom.) 


TUMORS.  369 

pretty  uniformly  throughout  the  growth,  or  they  may  be  much 
more  abundant  in  some  places  than  in  others.  The  cells  with  single 
nuclei,  among  which  the  giant-cells  are  found,  may  be  of  the 
spindle-shaped  variety,  or  they  may  be  polymorphic,  in  which  case 
cells  of  various  shapes  and  sizes  are  met  with. 

The  giant-cell  sarcomata  are  usually  derived  from  the  medulla 
of  bone.  They  constitute  the  most  common  form  of  epulis  (Fig. 
333),  and  frequently  attain  very  large  dimensions  when  they  take 

FIG.  333. 


Giant-cell  sarcoma  of  the  superior  maxilla;  epulis:  a,  large  giant-cell,  with  numerous 
nuclei ;  b,  tangential  section  of  a  similar  cell.  Aside  from  the  giant-cells,  the  growth  is 
composed  of  spindle-cells  and  a  moderate  amount  of  a  fibrous  intercellular  substance. 
The  tumor  was  removed  from  a  man  forty-one  years  of  age,  and  was  of  slow  growth, 
having  attained  the  size  of  a  filbert  in  two  and  a  half  years. 

their  origin  in  the  marrow  of  the  larger  bones,  such  as  the  femur 
or  tibia.  They  are  not,  however,  confined  to  bone,  but  may  occur 
in  other  situations ;  e.  g.,  the  breast. 

The  malignancy  of  giant-cell  sarcomata  must  be  estimated  in 
individual  cases  according  to  the  principles  already  elucidated. 

/.  MELANOSARCOMA. — Sarcomata  which  spring  from  pigmented 
tissues,  such  as  the  choroid  of  the  eye,  pigmented  moles,  etc.,  fre- 
quently show  a  pigmentation  of  their  constituent  cells,  the  pigment 
appearing  as  brown  granules  of  various  size  within  the  cytoplasm 
of  the  cells.  The  cells  are  not  all  equally  affected,  and  many  may 
be  seen  without  any  sign  of  pigmentation.  The  tumors  are  apt 
to  be  of  the  spindle-cell  or  large  round-cell  varieties,  and  are 

24 


370  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

FIG.  334. 


Melanosarcoma  of  the  skin.  (Ribbert.)  The  growth  is  an  alveolar  large  round-cell  sarcoma, 
containing  cells  that  have  undergone  a  pigmentary  degeneration.  Some  of  these  cells 
contain  so  much  pigment  that  the  cellular  constituents  are  invisible. 

considered  as  rather  more  malignant  than  the  non-pigmented  forms 
of  those  tumors  (Fig.  334). 


II.   THE   MUSCULAR  TUMORS. 

Muscular  fibres  of  either  the  smooth  involuntary  or  the  striated 
variety  may  enter  into  the  formation  of  tumors.  Tumors  made  up 
of  the  former  are  called  leiomyomata;  those  containing  striated 
muscle,  rhabdomyomata. 

1.  Leiomyoma. — The  cells  of  the  tissue  forming  leiomyomata  very 
closely  resemble  those  of  normal  smooth  muscular  tissue,  but  they 
may  show  a  greater  variation  in  size.  They  are  arranged  in  bundles, 
their  long  axes  parallel  to  each  other  ;  and  these  bundles  are  inter- 
woven in  such  a  way  that  sections  of  the  tumor  contain  longitudinal, 
oblique,  and  cross-sections  of  the  individual  fibres  (Fig.  335).  Between 
the  bundles  there  is  a  variable  amount  of  fibrous  tissue,  giving  sup- 
port to  the  bloodvessels  of  the  tumor.  This  fibrous  tissue  may  be 
so  abundant  as  to  form  a  large  element  in  the  structure  of  the  tumor, 
which  is  then  denominated  a  fibromyoma.  It  may,  also,  occasion- 
ally be  imperfectly  developed,  converting  the  growth  into  a  leio- 
myosarcoma.  The  muscular  tissue  may  undergo  a  hyaline  degen- 
eration and  become  the  seat  of  calcareous  infiltration,  or  the  cells 
may  be  the  seat  of  fatty  degeneration  with  subsequent  softening. 

Leiomyomata  arise  in  parts  which  normally  contain  smooth  mus- 


TUMORS. 


371 


FIG.  335. 


'^^^^^^^  ^ 


Leiomyoma  of  the  uterus.    (Birch-Hirschfeld.) 

cular  tissue.    They  are  common  in  the  uterus,  but  may  occur  in  the 

FIG.  336. 


Rhabdomyosarcoma  of  the  kidney  :  a,  a,  a,  imperfectly  developed  striated  muscle-fibres ;  6, 
tissue  composed  of  small  round  and  spindle-shaped  cells,  separated  by  considerable  deli- 
cate fibrous  intercellular  substance.  In  other  parts  of  the  growth,  which  was  the  size 
of  the  fist,  this  tissue  was  more  distinctly  sarcomatous  and  the  amount  of  muscular  tissue 
smaller.  The  child  from  which  this  tumor  was  removed  was  about  two  years  old. 

intestinal  walls,  the  urinary  tract,  or  the  skin.    When  pure,  or  when 
associated  with  fibrous  tissue  alone,  they  are  benign. 


372 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


2.  Rhabdomyoma. — The  striated  muscle-fibres  of  rhabdomyomata 
are  often  so  imperfectly  developed  that  they  are  difficult  of  recognition. 
They  are  much  more  attenuated  than  the  normal  fibres,  and  may  be 
reduced  to  very  narrow  and  tapering  structures  that  possess  only  traces 
of  striation.  Staining  with  eosin  will  often  aid  their  detection  among 


FIG.  337. 


Isolated  muscle-fibres  from  a  rhabdomyoma  of  the  oesophagus.  (Wolfensberger.)  a,  6, 
appearances  simulating  a  sarcolemma,  probably  due  to  adherent  fragments  of  the  inter- 
cellular substance. 

the  fibres  of  the  connective  tissue  surrounding  them,  as  it  stains  the 
contractile  substance  a  coppery-red.  The  nuclei  of  the  muscle-cells 
are  frequently  numerous,  and  may  occupy  the  centre  of  the  fibre, 
the  imperfectly  formed  contractile  substance  lying  at  the  periphery. 
In  some  rare  cases  the  tumor  is  composed  almost  exclusively  of 


TUMORS, 


373 


striated  muscle-fibres,  arranged  in  irregular,  interwoven  bands,  with 
a  little  vascular  fibrous  tissue  among  them.  In  other  cases  the 
muscular  fibres  are  sparsely  distributed  through  the  growth,  and 
can  often  be  found  only  after  a  prolonged  search.  In  these  cases 
the  tissue  in  which  the  muscle  is  situated  is  usually  some  variety  of 
sarcoma,  when  the  whole  tumor  is  known  as  a  rhabdomyosarcoma 
(Figs.  336,  337,  and  338).  Such  mixed  tumors  are  most  frequently 
found  in  the  genito-urinary  tract,  especially  in  the  kidney,  and  may 
attain  very  large  size.  They  are  apt  to  occur  in  the  early  years  of 

FIG.  338. 


Isolated  cells  from  a  rhabdomyoma  of  the  heart.    (Cesaris-Demel.) 

life,  and  are  probably  due  to  developmental  anomalies.  The  sarcom- 
atous  element,  which  is  usually  predominant,  gives  them  a  highly 
malignant  character. 

III.  THE  ANGIOMATOUS  TUMORS. 

Reference  has  already  been  made  to  the  manner  in  which  the 
bloodvessels  of  a  part  may  proliferate  under  the  influence  of  the 
inflammatory  process,  and  also  to  the  fact  that  when  tumors 
develop  the  bloodvessels  proliferate  in  a  similar  way  to  form  new 
vascular  areas  within  the  tumor,  from  which  the  latter  derives  its 
nourishment.  These  instances  of  proliferation  may  be  regarded  as 
the  natural  response  on  the  part  of  the  vascular  system  to  the  de- 
mand thrown  upon  it  by  the  formation  of  new  tissues.  In  a  general 
way,  they  are  limited  to  the  needs  of  the  tissues  which  they  supply. 
A  vascular  proliferation  may,  however,  take  place  irrespective  of 


374  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

any  such  demand,  and  continue  without  any  such  limitation.  In 
this  way  the  vascular  tumors,  or  angiomata,  are  produced.  We 
may  regard  them  as  springing,  not  from  a  single  tissue  or  an  adven- 
titious combination  of  tissues,  but  from  one  of  those  anatomical 
"  systems "  in  which  several  tissues  are  normally  associated  in  a 
definite  arrangement,  and,  under  normal  conditions,  develop  together 
to  form  well-defined  structures  distributed  throughout  the  body. 
There  are  three  such  systems  of  associated  tissues :  the  bloodvessels, 
the  lymphatic  system,  and  the  nervous  system.  Each  of  these  may 
enter  into  the  formation  of  an  apparently  purposeless  neoplasm, 
forming  the  hsemangiomata,  lymphangiomata,  and  neuromata.  Of 
these,  the  first  two  are  of  vascular  character  and  mesodermic  origin, 
and  their  consideration  naturally  follows  that  of  the  other  tumors 
arising  in  tissues  of  similar  embryonic  origin. 

1.  Hsemangioma. — The  bloodvessels  entering  into  the  formation 
of  hsemangiomata  are  usually  relatively  deficient  in  the  develop- 
ment of  their  muscular  coats.  They  resemble  large  capillaries 
which  have  been  reinforced  by  a  covering  of  fibrous  tissue.  The 
vessels  may  lie  with  their  walls  almost  in  contact  with  each  other, 
or  there  may  be  a  considerable  amount  of  interstitial  tissue  between 
them.  It  is  not  always  possible  to  decide  in  a  given  case  whether 
the  vessels  are  strictly  of  new  formation  or  not.  Masses  consisting 
essentially  of  bloodvessels  may  arise  through  dilatation  of  pre- 
existent  vessels,  with  atrophy  of  the  tissues  that  normally  lie  be- 
tween them.  This  is  the  origin  of  the  angiomata  of  the  liver,  and 
many  of  the  angiomata  of  the  skin  (nsevi)  are  explicable  in  the 
same  manner.  In  the  liver  the  capillaries  of  the  lobules  become 
dilated  and  their  walls  thickened,  the  parenchymatous  cells  between 
them  disappearing  by  atrophy,  and,  as  the  capillary  walls  come  in 
contact  and  exert  mutual  pressure,  they  may  undergo  atrophy,  per- 
mitting a  communication  between  their  lumina,  so  that  a  spongy 
mass  of  tissue  results,  with  large  cavities  filled  with  blood  (Fig. 
339).  Such  "cavernous  angiomata"  hardly  constitute  tumors  in  the 
restricted  sense  in  which  that  term  has  been  used  hitherto.  They 
are  rather  ectatic  states  of  the  vessels  normally  present  in  the  parts 
where  they  are  found. 

Somewhat  more  akin  to  the  true  tumors  are  the  masses  which 
arise  through  elongation  and  widening  of  the  vessels  of  a  part 
(aneurisma  racemosa),  for  in  this  case  there  is  a  real  reproduction 
or  growth  of  the  vessels. 


TUMORS. 


375 


Angiosarcomata  are  tumors  in  which  a  new  formation  of  blood- 
vessels with  a  sarcomatous  adventitia  springs  from  connective  tissue 
either  in  the  general  fibrous  structures  of  the  body  or  the  interstitial 
tissue  of  the  viscera.  Sections  of  these  tumors  sometimes  reveal 
thin-walled  vessels  with  a  distinct,  broad  zone  of  sarcomatous  tissue 
around  them,  resembling  an  enormously  thickened  adventitia  of 
embryonic  tissue  (Fig.  322).  In  other  cases  the  embryonic  tissue 
that  represents  the  adventitia  of  the  separate  vessels  is  fused  into 
a  mass  of  sarcomatous  tissue  lying  between  the  vessels.  The  tumor 

FIG.  339. 


Cavernous  hsemangioma  of  the  liver :  a,  substance  of  the  liver;  6,  fibrous  capsule  formed  at 
the  margin  of  the  angioma,  probably  the  result  of  a  chronic  productive  inflammation ; 
c,  space  filled  with  blood ;  d,  atrophic  wall  between  two  of  the  spaces  of  the  angioma. 

is  then  similar  in  structure  to  an  ordinary  sarcoma,  in  which  the 
vessels  are  more  abundant,  perhaps,  than  is  usual. 

When  the  angiomata  have  been  removed  by  operation  the  vessels 
are  usually  emptied  by  the  pressure  that  has  been  exerted  upon  their 
tissues  by  the  operative  manipulations.  This  condition  often  gives 
rise  to  puzzling  appearances,  when  the  endothelial  cells  of  the  vas- 
cular walls  are  swollen  or  richer  in  cytoplasm  than  normal  adult 
endothelium.  Sections  of  the  tumor  then  look  like  sections  through 
a  gland.  The  true  nature  of  the  tubules  can  generally  be  deter- 
mined by  the  appearance  of  the  lumina,  which  in  the  collapsed  ves- 
sels is  not  circular,  while  in  the  glands  it  is  nearly  so  if  the  section 


376  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

be  transverse  to  the  direction  of  the  tube.  In  glandular  tubules  the 
epithelial  cells  are  usually  well-defined  and  clearly  distinguishable 
from  each  other.  This  is  not  apt  to  be  the  case  in  immature  endo- 
thelium. 

2.  Lymphangioma. — What  has  already  been  said  with  respect  to 
the  hsemangiomata  applies  to  the  lymphangiomata.  Many  of  these 
tumors  appear  to  be  the  result  of  a  dilatation  of  the  lymphatic 
vessels  normally  present  in  the  tissues;  but  cases  may  arise  in 
which  there  is  a  real  reproduction  of  those  vessels.  The  spaces  in 
the  tumor  are  either  empty  and  collapsed,  or  they  contain  lymph 
and  not  blood.  The  walls  of  the  vessels  are  frequently  thickened 
by  the  production  of  fibrous  tissue  around  them. 


IV.  THE  EPITHELIAL  TUMORS. 

The  epithelium,  which  by  its  proliferation  gives  rise  to  tumors, 
may  be  situated  either  within  a  glandular  structure  of  the  body  or 
upon  one  of  its  free  surfaces,  such  as  the  skin  or  a  mucous  mem- 
brane. The  tumors  which  result  are  not  wholly  composed  of  epithe- 
lium. There  is  always  a  development  of  the  connective  tissue  of 
the  part,  furnishing  a  vascularized  nutrient  substratum  for  the 
epithelium.  The  epithelium  of  glandular  organs  may  give  rise 
to  two  sorts  of  tumors,  the  adenomata  and  the  carcinomata.  The 
stratified  epithelium  of  the  skin  and  some  of  the  mucous  membranes 
proliferate  to  form  the  epitheliomata. 

1.  Adenoma. — In  this  form  of  epithelial  tumor  there  is  a  more 
or  less  perfect  adherence  to  the  structure  of  a  normal  gland.  When 
adenomata  spring  from  the  epithelium  of  tubular  or  acinous  glands 
the  lobules  of  the  tumor  are  composed  of  tubes  or  acini  with  a 
distinct  lining  of  epithelium  enclosing  their  lumina  (Fig.  340).  But 
there  is  almost  always  some  departure  from  the  typical  structure 
of  a  gland ;  the  lobules  may  be  of  unequal  size  in  a  more  marked 
degree  than  is  usual,  the  character  of  the  epithelial  lining  may  be 
abnormal,  or  the  distribution  and  arrangement  of  the  lobules  may 
betray  an  abnormal  tendency  on  the  part  of  the  growth.  The 
latter  feature  is  exemplified  in  the  adenomata  of  the  rectum,  in 
which  the  new-formed  glandular  structure  is  apt  to  penetrate  the 
muscularis  mucosse  and  develop  abundantly  in  the  submucous  coat 
or  even  in  the  deeper,  muscular  tissues  of  that  part  of  the  in- 
testine. 


TUMORS. 


377 


The  adenomata  of  the  breast  deserve  a  rather  close  study.  A 
perfectly  simple  adenoma  of  this  gland  appears  to  be  a  very  rare 
growth.  There  is  nearly  always  an  association  with  diffuse  fibroma, 
forming  an  adenofibroma.  These  are  often  cystic,  an  accumulation 
of  a  serous  fluid  in  the  acini  causing  their  dilatation  (cystic  adeno- 
fibroma) (Fig.  341).  In  other  cases  the  fibromatous  tissue  grows 

FIG.  340. 


Adenoma  of  the  pancreas.  (Cesaris-Demel.)  The  atypical  nature  of  the  growth  is  revealed 
by  the  character  of  the  epithelial  cells,  their  arrangement  within  the  alveoli,  and  the 
disposition  of  the  latter  with  respect  to  each  other  and  the  interstitial  tissue. 

into  the  acini,  which  are  enlarged  to  receive  these  ingrowths  from 
their  walls.  The  ingrowing  masses  of  fibrous  tissue  are  covered 
with  epithelium  like  that  lining  the  rest  of  the  acinus,  a  fact  which 
would  be  expected  when  we  reflect  that  the  ingrowth  is  a  sort  of 
intrusion  of  the  wall  of  the  acinus  itself.  Sometimes  these  in- 
growths have  a  papillomatous  character,  but  more  frequently  they 
have  a  globular  form  and  give  off  globular  branches  within  the 
acinus.  Sections  of  such  growths  often  have  a  complicated  appear- 
ance. Irregular  and  branching  bands  of  epithelium  are  seen  cours- 
ing through  a  mass  of  fibrous  tissue.  They  are  the  epithelial 
linings  of  the  acini  which  have  baen  brought  into  contact  by  the 
ingrowths  of  fibrous  tissue,  obliterating  the  lumina  of  the  acini. 


378  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

Part  of  this  epithelium  is,  therefore,  that  which  may  be  said  to  line 
the  dilated  acini ;  the  rest,  that  which  covers  the  fibrous  tissue 
which  has  grown  into  the  acini  and  caused  contact  of  the  epithe- 
lial layers  with  obliteration  of  the  lumina.  Where  the  pedicles 
of  these  ingrowths  are  small,  sections  may  contain  rings  of  epithe- 
lium surrounding  an  isolated  mass  of  fibrous  tissue  if  the  section 
does  not  include  the  pedicle  of  that  particular  ingrowth  (Fig.  342). 

FIG.  341. 


Adenofibroma  of  the  breast.    (Birch-Hirschfeld.)    The  section  shows  a  tendency  toward 
cystic  dilatation  of  the  glandular  acini. 

If  the  tumor  is  examined  macroscopically,  the  ingrowths  may 
often  be  lifted  from  the  acini  in  which  they  lie.  These  tumors 
have  received  the  name  "  intracanalicular  adenofibroma."  They 
must  be  carefully  distinguished  from  the  scirrhous  carcinomata  of 
the  breast,  which,  upon  superficial  examination,  they  somewhat 
resemble. 

In  examining  sections  of  the  breast  with  a  view  to  determining 


379 


Intracanalicular  adenofibroma  of  the  breast.  (Kaufmann.)  In  this  example  the  lumina  of 
the  acini  have  not  been  obliterated,  and  a  correct  interpretation  of  the  appearances  pre- 
sents no  difficulty. 

FIG.  343. 


Section  from  the  mammary  gland  of  a  nullipara,  aged  eighteen ;  moderately  magnified. 

(Altmann.) 


380 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


the  question  of  the  existence  of  a  tumor  the  normal  variations  in 
that  organ  must  be  carefully  considered.  In  the  description  of  the 
normal  mammary  gland  it  was  stated  that  the  microscopical  struct- 
ure differed  greatly  according  to  the  functional  activity  of  the 


Section  from  the  mammary  gland  of  a  nullipara,  aged  eighteen ;  more  highly  magnified. 

(Altmann.) 

organ.  It  is  proper  to  recur  to  those  differences  in  this  connection 
because  of  the  importance  of  many  of  the  mammary  tumors,  that 
gland  being  one  of  the  common  sites  of  carcinoma  and  adenoma. 

FIG.  345. 


Section  from  the  mammary  gland  of  a  nullipara,  aged  twenty-two ;  slightly  magnified. 

(Altmann.) 

In  Figs.  343  to  350  sections  of  the  gland  in  various  stages  of 
development  and  involution  are  represented.  Figs.  343  to  346 
represent  sections  from  the  breasts  of  nulliparse,  aged  respectively 
eighteen  and  twenty-two  years.  The  parenchyma  of  the  gland  has 


TUMOES. 


381 


a  general   tubular   structure,   the  acini  being  in  an  undeveloped 
state. 

Figs.  347  and  348  show  sections  of  the  mammary  gland  of  a 


Section  from  the  mammary  gland  of  a  nullipara,  aged  twenty-two ;  more  highly  magnified. 

(Altmann.) 

woman,  aged  thirty-eight,  who  had  born  five  children.     The  sec- 
tions were  taken  at  the  beginning  of  functional  activity  of  the  gland. 
Figs.  349  and  350  represent  involuted  mammary  glands,  respec- 


Section  of  the  mammary  gland   at  the   beginning  of  lactation;   moderately  magnified. 

(Altmann.) 

tively  nine  and  fourteen  months  after  functional  activity  had  been 
arrested. 

Adenomata  are  usually  of  benign  character ;  but,  as  is  the  case 
with  all  neoplasms,  it  will  not  do  to  conclude  that  a  growth  is  harm- 
less merely  because  it  can  be  included  in  a  group  of  tumors  that  are 
usually  benign.  The  evidence  as  to  its  tendencies  revealed  by  the 


382 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


structure  of  each  individual  tumor  must  be  carefully  weighed  before 
a  conclusion  as  to  its  benignancy  or  malignancy  is  reached.  Aden- 
omata are  benign  in  proportion  as  they  adhere  to  the  structure  of  a 
normal  gland  of  the  type  which  they  simulate.  They  approach 


FIG.  348. 


Section  of  the  mammary  gland  at  the  beginning  of  lactation ;  more  highly  magnified. 

(Altmann.) 

malignancy  when  they  become  atypical  and  show  a  tendency  to 
infiltrate  their  surroundings.  The  adenomata  of  the  rectum, 
already  referred  to,  are  likely  to  prove  malignant,  and  in  their 
structure  they  show  a  departure  from  the  simple  type  of  tubular 
gland  normally  present  in  the  rectum  (Fig.  351).  They  also  dis- 

FIG.  349. 


'Section  of  the  mammary  gland  in  a  state  of  involution.    (Altmann.)    From  a  woman,  aged 
twenty-five,  nine  months  after  the  cessation  of  functional  activity. 

play  a  marked  tendency  to  infiltrate  their  surroundings.  While 
they  belong  to  a  group  of  generally  benign  tumors,  they  possess 
an  atypical  structure  and  a  power  of  infiltration  that  reveal  their 
malignant  character. 

2.  Carcinoma. — The  epithelium   of  developing  secreting  glands 


TUMORS. 


383 


first  appears  as  little  solid  columns  of  epithelial  cells,  which  spring 
from  the  epithelium  covering  the  part  and  penetrate  the  underlying 


FIG.  350. 


Section  of  mammary  gland  in  a  state  of  involution.    (Altmann.)    From  a  woman,  aged 
thirty-two,  fourteen  months  after  functional  activity  had  ceased. 

tissues  (see  Fig.  181).   These  columns  subsequently  become  hollowed 
to  form  tubes  or  sacs  lined  with  secreting  epithelium.     In  carci- 

FIG.  351. 


Infiltrating  adenoma  of  the  rectum.  (Hansemann.)  The  figure  represents  alveoli  of  atypical 
character,  differing  greatly  from  the  normal  glandular  structures  of  that  part  of  the  body. 
The  section  does  not  include  the  infiltrating  portion  of  the  growth. 

nomata  the  embryonic  state  of  gland-formation  is  simulated  by  the 
growth,  so  that  a  carcinoma  may  be  considered  as  formed  upon  the 


384  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

type  of  a  developing  gland  in  the  same  sense  as  a  sarcoma  is 
analogous  to  developing  connective  tissue. 

As  a  result  of  this  structure,  sections  of  carcinomata  appear  to 
be  composed  of  alveoli,  which  are  filled  with  epithelial  cells  and 
have  walls  of  fibrous  tissue.  The  character  of  the  epithelium 
depends  chiefly  upon  the  variety  from  which  the  tumor  sprang. 
The  sizes  of  the  alveoli  and  the  amount  of  fibrous  tissue  that  sepa- 
rates them  from  each  other  vary  in  different  tumors,  and  the  carci- 
nomata are  divided  into  rather  ill-defined  groups,  according  to  the 
relative  abundance  of  the  epithelium  they  contain  as  compared  with 
the  amount  of  fibrous  tissue  They  are  also  subdivided  according  to 
the  character  of  the  epithelium. 

a.  MEDULLARY  CARCINOMATA  (Fig.  352)  are  those  in  which 

FIG.  352. 


Medullary  carcinoma  of  the  mammary  gland.  (Hansemann.)  The  stroma  of  the  tumor  is 
here  reduced  to  a  minimal  amount  of  areolar  tissue  containing  the  vascular  supply  of 
the  growth. 

there  is  the  least  amount  of  fibrous  tissue.  The  alveoli  are  usually 
large  and  filled  with  polyhedral  cells.  The  fibrous  tissue  of  the 
alveolar  walls  may  be  so  reduced  in  amount  as  virtually  to  serve 
merely  as  a  support  to  the  bloodvessels  it  contains.  Such  tumors 
are  soft,  of  rapid  growth,  and  very  prone  to  degenerative  changes 
and  metastasis. 

6.  SIMPLE  CARCINOMATA  contain  about  an  equal  amount  of  epi- 
thelial and  fibrous  tissues  (Fig.  353). 

c.  SCIRRHOUS  CARCINOMATA  (Fig.  354)  are  characterized  by 
small  alveoli  separated  by  large  quantities  of  dense  fibrous  tissue. 


TUMORS. 


385 


The  latter  may  so  greatly  preponderate  over  the  epithelium  that 
there  is  a  possibility  of  mistaking  the  tumor  for  a  simple  fibroma. 


FIG.  353. 


Carcinoma  simplex  mammee.  (Kaufmann.)  In  this  growth  the  stroma  is  well  developed  and 
divides  the  tumor  into  a  number  of  intercommunicating  alveoli,  filled  with  epithelial 
cells. 

Care  must  be  taken  not  to  confound  these  carcinomata  with  the 
intracanalicular  adenofibromata  already  described.    In  the  carcinoma 


FIG.  354. 


m    t 


Scirrhous  carcinoma  of  the  breast.    (Ribbert.)    The  bulk  of  the  section  Is  composed  of  dense 
fibrous  tissue,  in  which  there  area  few  rows  of  epithelial  cells,  a. 

there  is  no  ingrowth  of  fibrous  tissue  into  the  alveoli,  as  in  the 
case  of  the  adenofibroma.     The  development  of  the  fibrous  tissue  in 


2;') 


386 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


these  cancers  is  probably  induced  by  the  proliferation  of  the  epi- 
thelium, but  it  sometimes  happens  that  the  fibrous  tissue  form- 
ing the  stroma  of  the  tumor  compresses  the  epithelium  after  the 
growth  has  attained  a  certain  stage  of  maturity,  and  causes  an 
atrophy  of  its  cells  (atrophying  carcinoma).  As  a  result  the  tumor 
may  suffer  a  diminution  in  size,  but  this  shrinkage  occurs  only  in 
the  older  parts  of  the  tumor ;  the  peripheral  portions  continue  to 
grow.  It  is  no  indication  of  a  spontaneous  cure. 

Carcinomata  are  malignant,  but  differ  in  the  rapidity  of  their 
clinical  course.  Those  which  are  softer — i.  e.,  contain  a  larger  pro- 
portion of  epithelium — are  of  more  rapid  growth  than  the  harder 
varieties ;  but  they  all  tend  to  infiltrate  their  surroundings  and  are 
liable  to  metastasis.  The  usual  mode  of  infiltration  is  for  the  pro- 
liferating epithelium  to  penetrate  the  lymph-spaces  or  lymphatic 
vessels  of  the  neighboring  tissues.  The  cells  may  advance  as  solid 

FIG.  355. 


Carcinoma  invading  adipose  tissue.  The  figure  represents  a  section  of  the  fat  surrounding 
the  breast  in  a  case  of  mammary  carcinoma.  Masses  of  epithelium  are  present  in  the 
lymphatic  spaces  of  the  areolar  tissue  between  the  fat-cells.  The  nuclei  of  some  of  the 
epithelial  cells  show  imperfectly  preserved  karyokinetic  figures.  To  the  right,  above,  is 
a  group  of  four  epithelial  cells  surrounded  by  a  round-cell  (inflammatory)  infiltration. 

columns  pushed  out  from  the  growth  along  these  lymph-channels, 
or  cells  may  become  detached  from  the  main  growth  and  be  car- 
ried by  the  lymph-current  for  a  greater  or  less  distance  from  the 
original  tumor,  to  find  lodgement  in  some  situation  in  which  the 
conditions  may  be  favorable  for  their  continued  multiplication 


TUMORS. 


387 


(Fig.  355).  The  connective  tissue  of  the  new  site  is  then  induced 
to  proliferate  and  form  the  cancerous  stroma.  If  this  transfer  of 
cells  is  only  for  a  short  distance,  the  process  is  called  infiltration ; 
if  the  distance  is  greater,  metastasis.  It  appears,  then,  that  meta- 
stasis usually  occurs  through  the  lymphatics,  as  it  is  through  them 
that  the  natural  extension  of  the  carcinoma  takes  place.  The  cells 
that  gain  entrance  to  the  lymphatic  vessels  are  most  likely  to  be 
arrested  in  the  nearest  lymph-node,  giving  rise,  if  they  multiply, 

FIG.  356. 


Secondary  carcinoma  of  a  lymph-gland.  (Ribbert.)  Epithelial  cells  from  the  primary  car- 
cinoma have  been  carried  by  the  lymph-current  to  the  node,  where  they  have  been 
arrested  in  the  lymph-sinus.  Here  they  have  continued  to  proliferate,  giving  origin  to  a 
secondary,  or  metastatic,  nodule  of  carcinoma. 

to  a  secondary  tumor  within  it  (Fig.  356).  These  secondary  tumors 
in  the  lymph-nodes  may,  after  a  period  of  development,  furnish 
cells  for  a  still  wider  metastasis. 

Metastasis  through  the  lymphatics  is  not  the  only  means  by 
which  carcinomata  may  become  generalized.  They  may  infiltrate 
the  walls  of  bloodvessels,  usually  veins,  and  finally  discharge 
cells  into  the  blood,  giving  rise  to  cancerous  embolism  with  a  gen- 
eral diffusion  of  secondary  nodules  in  the  first  capillary  district 
through  which  the  blood  is  distributed.  In  this  way  multiple 
carcinomata  of  the  liver  or  lung  are  produced.  The  secondary 
carcinomatous  nodules  usually  resemble  the  primary  tumor,  espe- 
cially as  regards  the  character  of  the  epithelium ;  but  the  relative 
amount  of  stroma  is  very  frequently  considerably  less.  A  scirrhous 
carcinoma  may  give  rise  to  secondary  nodules  of  medullary  car- 
cinoma. The  distinction  between  the  different  varieties  is,  therefore, 
more  descriptive  than  essential. 

Carcinoma  is  apt  to  occasion  the  development  of  a  cachexia  in 
the  patient.  The  reason  for  this  is  probably  to  be  sought  in  the 


388  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

absorption  of  the  products  of  metabolism  from  the  tumor,  rather 
than  in  the  abstraction  of  nourishment  from  the  organism.  Epi- 
thelium, especially  of  the  glandular  form,  is  a  tissue  of  great 
chemical  activity,  and  in  carcinomata  there  is  no  special  outlet  for 
the  products  of  that  activity,  such  as  is  furnished  by  the  ducts  of 
normal  glands.  It  may,  therefore,  be  reasonable  to  infer  that  the 
products  resulting  from  the  chemical  activities  of  the  epithelial  cells 
must  be  absorbed  into  the  system,  and  that  they  may  injuriously 
affect  the  nutrition  and  the  functions  of  distant  organs.  Carcin- 
omata are  ,also  liable  to  undergo  degenerations,  the  products  of 
which  may  be  deleterious  to  the  organism. 

A  form  of  carcinoma  which  differs  somewhat  in  appearance  from 
those  that  have  been  mentioned,  though  it  is  of  essentially  the  same 
nature,  is  the  "  colloid  carcinoma  "  (Fig.  357).  This  variety  springs 


Colloid  carcinoma.  (Ribbert.)  The  section  represents  a  delicate  stroma  of  areolar  tissue 
separating  alveoli,  which  are  not  filled  with  cells,  but  contain  the  products  of  their 
mucous  degeneration  and  a  few  cells  which  have  not  yet  undergone  complete  destruc- 
tion. 

from  epithelium  that  under  normal  conditions  secretes  mucus. 
This  function  renders  the  cells  of  the  cancer  particularly  liable  to 
mucoid  degeneration,  and  this  may  be  so  extensive  as  to  destroy  all 
or  nearly  all  of  the  cells  in  some  of  the  alveoli  of  the  tumor,  con- 
verting them  into  a  soft  mucous  mass  that  usually  does  not  appear 
quite  uniform  under  the  microscope.  The  epithelial  cells  are  gen- 
erally of  columnar  form,  arranged,  at  the  periphery  of  the  alveoli, 
with  their  ends  in  contact  with  the  alveolar  wall.  This  arrange- 


TUMORS. 
KKJ.  358. 


389 


s  P" 

^  *— . 


Adeiiocarcinoma  of  the  liver,  (v.  Henkelou.)  o,  normal  liver-cell ;  b,  modified  epithelial 
cell  entering  into  the  formation  of  tin-  neoplasm;  r,  normal  nucleus;  </,  nucleus  abnor- 
mally rich  in  chromatin  preparatory  to  cell-division  ;  e,  fat-globule  in  the  epithelium  of 
the  tumor,  showing  a  tendency  to  fatty  degeneration. 


390  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

ment  of  the  cells  is  often  strikingly  shown  in  secondary  tumors  of 
the  lung,  in  which  the  cells  have  appropriated  the  pulmonary  alveoli 
for  their  stroma. 

It  occasionally  happens  that  the  connective  tissue  that  forms  the 
stroma  of  a  carcinoma  does  not  progress  in  its  development  to  the 
formation  of  fibrous  tissue,  but  assumes  a  sarcomatous  character. 
Such  tumors  are  called  a  carcinoma  sarcomatosum."  A  more  fre- 
quent association  is  one  of  carcinoma  with  adenoma,  "  adenocar- 
cinoma  "  (Fig.  358).  In  these  neoplasms,  either  the  two  forms  of 

FIG.  359. 


.^W 

Epithelioma  of  the  cheek.     (Ernst.)    a,  delicate  tongues  of  epithelium  extending  into  the 
lymphatics  of  the  part ;  b,  c,  larger  masses  of  epithelium  containing  pearl-bodies. 

epithelial  tumor  may  occupy  different  portions  of  the  growth,  or 
the  general  character  of  the  growth  may  be  that  of  a  rather  typical 
carcinoma — i.  e.,  a  carcinoma  showing  indications  of  a  development 
beyond  the  undiiferentiated  state  analogous  to  an  embryonic  gland 
— or  that  of  a  rather  atypical  adenoma. 


TUMORS. 


391 


3.  Epithelioma. — This  tumor  is  essentially  a  carcinoma  springing 
from  stratified  epithelium.  Under  normal  circumstances  the  cells 
of  this  variety  of  epithelium  multiply  in  its  deeper  layers  and  are 
gradually  pushed  toward  the  surface  while  they  mature.  Epithe- 
liomata  are  produced  when  the  proliferating  cells  penetrate  the 
underlying  tissues  in  columns,  which  ramify  through  those  tissues 
and  ultimately  appear  as  the  contents  of  well-defined  alveoli  sur- 
rounded by  a  fibrous-tissue  stroma  similar  to  that  present  in  car- 
cinomata  (Fig.  359).  The  epithelium  retains  its  general  characters  : 
the  cells  at  the  periphery  of  the  alveoli  multiply,  and  either  further 

FIG.  360. 


Epithelial  pearl-body  from  an  epithelioma  of  the  lip :  a,  pearl-body ;  6,  surrounding  epithe- 
lium, forming  one  of  the  epitheliomatous  tongues  or  columns;  c,  round-cell  infiltra- 
tion of  the  contiguous  fibrous  tissue. 

infiltrate  the  surrounding  tissues  or  crowd  each  other  toward  the 
centres  of  the  alveoli  as  they  increase  in  number  and  size.  Here 
they  eventually  undergo  keratoid  transformation,  just  as  they  would 
upon  the  surface  of  the  normal  epithelium  ;  only  here  they  are 
crowded  toward  the  centres  of  the  alveoli,  where  the  horny  scales 
become  imbricated  to  form  globular  masses,  called  epithelial  "  pearl- 
bodies  "  (Fig.  360).  The  epitheliomata  may  penetrate  into  the 
lymphatics  and  be  subject  to  metastasis  in  a  manner  entirely  com- 
parable to  that  already  described  above.  They  are,  therefore, 
malignant,  though  of  slower  growth  than  the  medullary  or  simple 
carcinomata,  at  least  during  the  early  stages  of  their  development. 
It  should  always  be  borne  in  mind,  when  considering  the  prog- 


392  HISTOLOGY  OF  THE  MORBID  PROCESSES. 

nosis  in  a  case  of  carcinoma  or  epithelioma,  that  metastasis  may 
take  place  while  the  primary  growth  is  still  of  very  small  size, 
even  before  attention  has  been  called  to  the  existence  of  a  tumor. 
An  examination  of  the  peripheral  portion  of  the  growth  will  often 
throw  considerable  light  upon  the  probability  that  this  has  occurred, 
by  revealing  an  extension  of  epithelial  cells  into  the  lymphatics  of 
the  surrounding  tissues.  Cases  of  speedy  recurrence  of  such  a 
growth  after  operation  are  really  cases  in  which  tissues  that  have 
thus  been  infiltrated  have  not  been  completely  removed. 

Much  has  been  written  within  late  years  advocating  the  theory 
of  a  parasitic  causation  of  carcinomata  and  epitheliomata.  The 
appearances  which  have  led  to  this  belief  are  probably  due  to 
degenerative  or  morbid  processes  within  the  epithelial  cells  of  the 
tumor,  and  not  to  the  presence  of  parasites ;  but  further  study  of 
this  subject  may  show  that  parasites  have  the  power  of  causing 
rejuvenescence  of  cells  and  an  emancipation  from  the  ordinary 
restraints  that  regulate  their  development. 

4.  Cystoma. — Attention  has  been  called  to  the  cystic  adenomata 
of  the  mamma.  Similar  cysts  may  occur  in  other  regions  through 
dilatation  of  cavities  normally  present  in  the  tissues  by  some  fluid, 
usually  of  a  serous  character.  It  is  best  to  exclude  cystic  growths 
in  which  the  cystic  character  is  evidently  a  secondary  feature  of  the 
tumor,  or  where  a  cyst  arises  from  the  retention  of  a  secretion  or  is 
due  to  the  accumulation  of  a  fluid  in  a  normal  cavity,  from  the 
group  of  tumors  that  are  essentially  cystic.  Thus,  for  example, 
simple  hydrops  folliculorum  of  the  ovary  should  not  be  classed  with 
the  cystic  tumors  of  that  organ. 

The  ovary  is  the  favorite  site  for  cystic  tumors  of  new  formation, 
which  may  contain  only  a  single  cavity  (unilocular)  or  several  cav- 
ities (multilocular).  Histologically,  they  may  be  grouped  in  three 
divisions :  1,  simple,  in  which  the  walls  of  the  cyst  are  smooth  and 
covered  with  epithelium ;  2,  papillary,  in  which  there  are  ingrowths 
from  the  walls  of  the  cysts  into  their  cavities,  either  simple  or  branch- 
ing (Fig.  361) ;  and,  3,  dermoid,  which  contain  structures  simulating 
the  normal  skin  :  hair,  imperfectly  developed  teeth,  or  other  highly 
differentiated  tissues,  such  as  bone,  etc.  In  the  first  two  forms  the 
fluid  in  the  cystic  cavities  may  be  serous,  mucoid,  or  colloid  ;  fre- 
quently it  is  different  in  the  various  cavities  of  the  tumor.  In  der- 
moid cysts  there  is  often  a  greasy  substance,  similar  to  the  sebum 
of  the  skin,  derived  from  sebaceous  glands  in  the  cutaneous  struct- 


TUMORS. 
FIG.  361. 


393 


%j*e. 

''  " 


--" 


Section  from  a  papillary  cystoma  of  the  ovary.  (Birch-Hirschfeld.)  Part  of  the  wall  sepa- 
rating two  cystic  cavities  is  represented.  From  this  wall,  papillary  ingrowths  arise, 
which  project  into  the  cavity  of  the  cyst.  They  are  composed  of  a  delicate  areolar  tissue 
covered  with  columnar  epithelium  similar  to  that  lining  the  cysts. 

ures  of  the  growth.      Similar  dermoid  cysts  occasionally  develop 
from  the  skin,  but  are  usually  lined  with  merely  an  epidermis,  the 

FIG.  362. 


Gilomata  of  the  brain.    (Stroebe.)    Composed  of  glia-cells  of  small  type,  with  fine 

processes. 


394 


HISTOLOGY  OF  THE  MORBID  PROCESSES. 


scales  from  which  accumulate  in  the  cavity  of  the  tumor,  where 
they  may  be  mixed  with  sebum  (wens). 

5.  Glioma. — The  neuroglia,  originally  of  epithelial  origin  from 


FIG.  363. 


Gliomata  of  the  brain.  (Stroebe.)  Mixed  type,  containing  cells  like  those  in  Fig.  362,  but 
also  large  branching  cells  simulating  ganglion-cells,  "glioma  gangliocellulare." 

In  sections  of  gliomata  stained  by  the  methods  in  more  general  use  the  delicate  processes  are 
often  not  visible,  but  the  nuclei  are  prominent.  The  tumor,  therefore,  appears  highly 
cellular  with  a  finely  granular  material  (the  unstained  processes)  between  the  cells. 

the  ectoderm,  may  proliferate  to  form  tumors,  called  gliomata. 
These  diifer  in  their  structure  according  to  the  variations  in  type 
presented  by  the  glia-cells  composing  them  (Figs.  362  and  363). 


V.  PAPILLOMATA. 

Before  leaving  the  subject  of  tumors  it  will  be  necessary  to 
devote  a  few  words  to  the  consideration  of  growths  that  cannot  be 
considered  as  primarily  arising  from  either  epithelium  or  connective 
tissues.  The  papillomata  are  examples  of  such  growths.  These 
are  over-developments  of  papillary  structures  normally  present,  or 
spring  from  mucous  surfaces  where  such  structures  are  normally 
either  not  present  or  are  but  poorly  developed. 


TUMORS.  395 

A  papilloma  consists  of  vascularized  fibrous  or  areolar  tissue 
springing  from  a  surface  which  is  covered  with  epithelium.  The 
denser  forms  which  occur — e. g.,  upon  the  skin — constitute  "warts"  ; 
but  much  more  delicate  papillomata  may  spring  from  mucous  mem- 
branes, such  as  that  of  the  bladder,  and  are  then  known  as  villous 
tumors  or  villous  papillomata.  In  many  cases  the  denser  forms  of 
papilloma  appear  to  be  hypertrophies  due  to  irritation.  But  papil- 
lomata which  seem  to  be  true  neoplasms  or  tumors  in  the  restricted 
sense  of  that  term  hitherto  employed  appear  to  be  among  the  possi- 
bilities of  morbid  development. 


PART  III. 
HISTOLOGICAL   TECHNIQUE. 


CHAPTER  XXVI. 

PRACTICAL  SUGGESTIONS  FOR  THE  CARE  AND  USE  OF 
THE  MICROSCOPE.— MICROSCOPICAL  TECHNIQUE. 

IN  selecting  a  microscope  the  following  considerations  are  of 
importance  : 

The  stand  should  be  supported  on  three  points  and  rest  firmly  on 
the  table ;  have  a  rack-and-pinion  coarse  adjustment,  and  a  fine 
adjustment  free  from  all  loss  of  motion.  It  is  rarely  used  in  an 
inclined  position,  and  a  jointed  stand  is  unnecessary.  A  triple 
nose-piece,  or  revolver,  is  a  great  convenience,  and  an  Abbe  con- 
denser with  iris-diaphragm  is  almost  indispensable. 

Three  objectives  are  needed :  a  Leitz  No.  3  or  No.  4,  No.  7,  and 
TVth  or  y^th  oil  immersion,  or  their  equivalents  of  other  manu- 
facture, are  suitable  powers  for  general  use.  Two  oculars,  No.  2 
and  No.  4,  will  answer. 

The  microscope  should  be  protected  from  direct  sunlight  and  acid 
fumes,  and  be  kept  in  a  dry,  moderately  cool  place.  "When  not  in 
use  it  should  be  covered  or  placed  in  its  case,  to  protect  it  from 
dust.  If  the  lenses  become  dirty,  they  may  be  wiped  with  a  soft, 
clean  cloth  or  Japanese  paper,  either  dry  or  moistened  with  water, 
and  followed  by  a  dry  cloth  or  paper.  Balsam  or  cedar  oil  may  be 
removed  with  a  cloth  or  soft  paper  moistened  with  xylol,  after  which 
the  parts  should  be  carefully  wiped  dry. 

In  making  microchemical  tests  special  care  should  be  taken  not 
to  let  the  reagents  come  in  contact  with  the  objectives. 

Objects  should  always  be  examined  in  a  liquid,  unless  there  is 
some  special  reason  for  examining  them  in  a  dry  state  ;  and  should 
be  covered  with  a  cover-glass,  unless  a  cursory  inspection  with  a 
very  low  power  is  all  that  is  required. 

397 


398  HISTOLOGICAL  TECHNIQUE. 

In  studying  a  specimen  always  use  the  lowest  power  that  will 
reveal  the  structures  it  is  desired  to  see ;  and,  in  any  event,  use 
a  low  power  first,  to  get  a  general  idea  of  the  topography  of  the 
specimen.  In  this  way  the  portions  for  more  minute  study  can  be 
readily  selected,  with  a  great  saving  of  time. 

The  proper  illumination  of  the  specimen  is  just  as  important  as 
careful  focussing.  If  the  Abbe  condenser  is  in  use,  employ  the 
plane  surface  of  the  mirror  during  the  day ;  either  the  plane  or  the 
concave  surface  when  artificial  light  is  used,  selecting  the  surface 
which  causes  less  glare.  The  iris-diaphragm  should  be  kept  ad- 
justed so  as  to  give  the  best  definition  of  the  specimen  under  exam- 
ination when  the  latter  is  in  focus.  It  will  be  found  that  when 
colorless  objects  are  examined  a  small  opening  gives  the  clearest 
picture,  while  with  colored  objects  a  larger  opening  is  preferable. 
A  small  diaphragm  serves  to  bring  out  the  "structure-picture"  ;  a 
large  diaphragm,  the  "  color-picture  "  (see  p.  402). 

A  bottle  of  oil  of  cedar-wood,  having  approximately  the  same 
refractive  index  as  the  glass  from  which  the  cover-glasses  are  made, 
is  furnished  with  the  immersion-objectives.  When  these  are  used 
a  drop  of  this  oil  is  placed  on  the  cover,  and  the  end  of  the  objec- 
tive immersed  in  this  drop.  This  arrangement  permits  the  light  to 
pass  from  the  object  to  the  bottom  lens  of  the  objective  without  sen- 
sible refraction,  increasing  the  amount  of  light  entering  the  objec- 
tive, the  sharpness  of  definition,  and  the  purity  of  the  color-picture. 
When  the  lens  has  been  used  the  oil  should  be  removed  with  a  soft 
cloth  or  Japanese  paper.  The  oil  on  the  cover  may  be  wiped  off  at 
once,  or  it  may  be  allowed  to  dry  and  then  removed  with  a  cloth 
moistened  with  xylol. 

Microscopical  Measurements. — These  may  be  made,  with  a  fair 
degree  of  accuracy,  by  means  of  an  eye-piece  micrometer-scale. 
This  is  a  ruled  disc  of  glass  that  can  be  placed  upon  the  diaphragm 
within  the  ocular,  where  its  scale  should  be  well  defined  when  seen 
through  the  upper  lens  of  the  eye-piece.  Special  micrometer  ocu- 
lars are  made  which  permit  of  focussing  the  scale,  but  these  are 
unnecessary  if  the  diaphragms  of  the  ordinary  oculars  are  in  the 
right  places  within  the  eye-piece  tubes.  The  value  of  the  divisions 
of  the  eye-piece  micrometer-scale  must  be  determined  by  comparing 
it  with  the  scale  of  a  micrometer-slide  which  is  placed  upon  the 
stage  of.  the  microscope.  These  scales  usually  consist  of  1  mm. 
divided  into  hundredths,  and  the  eye-piece  scale  will  have  dif- 


MICROSCOPICAL   TECHNIQUE.  399 

ferent  values  for  each  combination  of  lenses  used  and  for  every 
variation  in  the  length  of  the  microscope-tube.  The  unit  for  micro- 
scopical measurements  is  one-thousandth  of  a  millimeter,  or  one- 
millionth  of  a  meter ;  it  is  called  a  "  micrometer/7  and  is  desig- 
nated by  the  Greek  letter  //.  One  division  of  the  micrometer-slide 
mentioned  above  would,  therefore,  equal  10  {*.  From  these  data  it 
is  possible  to  calculate  the  value  of  each  division  of  the  eye-piece 
micrometer-scale  in  terms  of  fj.  for  each  combination  of  lenses,  the 
length  of  the  microscope-tube  being  fixed.  (Most  Continental 
stands  and  many  American  stands  have  graduated  tubes,  and  the 
objectives  are  constructed  for  a  standard  tube-length  of  160  milli- 
meters.) 

It  is  well  for  the  student  to  get  into  the  habit  of  estimating  the 
sizes  of  the  objects  he  examines.  A  good  standard  for  mental  com- 
parison is  the  diameter  of  the  unaltered  red  blood -corpuscle,  which 
is  about  7.5  /*. 

MICROSCOPICAL  TECHNIQUE. 

Useful  preparations  for  study  under  the  microscope  may  be  pre- 
pared from  tissues  in  one  of  three  ways :  1,  simple  scrapings  of  the 
tissues  may  be  mounted  on  a  slide  in  the  fluids  derived  from  the 
tissues  themselves,  or  in  a  neutral  solution — e.  g.,  0.75  per  cent,  salt 
solution  ;  2,  the  tissue-elements,  cells,  and  intercellular  fibres,  etc., 
may  be  separated  from  each  other  by  treatment  with  some  macerat- 
ing-fluid — e.  g.,  very  weak  chromic  acid  (1  : 10,000),  36  per  cent, 
caustic  potash,  ^  alcohol ;  3,  sections  of  the  tissue  may  be  prepared 
either  while  they  are  fresh,  with  a  razor  or  a  freezing-microtome,  or 
after  hardening. 

The  first  method  has  a  limited  application.  It  is  serviceable 
only  when  the  tissue-elements  are  so  loosely  held  together  that  they 
readily  separate  from  each  other  and  can  be  examined  in  an  isolated 
condition.  This  is  the  case  with  a  considerable  number  of  tumors, 
the  superficial  tissues  of  mucous  membranes,  the  spleen,  etc.  If 
the  inside  of  the  cheek  be  scraped  with  the  finger-nail,  and  the 
material  thus  removed  be  diluted  with  saliva,  placed  upon  a  slide, 
and  covered  with  a  cover-glass,  the  squamous  epithelial  cells  lining 
the  cavity  of  the  mouth  will  be  readily  seen  in  an  isolated  state. 
An  appropriate  dye  may  now  be  introduced  under  the  cover,  and  by 
its  means  the  nuclei  of  the  cells  stained,  thus  bringing  them  into 
clearer  view. 


400  HISTOLOGICAL   TECHNIQUE. 

When  a  simple  scraping  of  the  natural  or  freshly  cut  surface  does 
not  yield  useful  preparations,  showing  isolated  tissue-elements,  some 
process  of  maceration  may  be  employed.  Bits  of  the  tissue  are 
soaked  for  a  time  in  some  solution  that  serves  to  soften  the  cement- 
substances  lying  between  the  elements  of  the  tissues,  so  that  they 
may  be  easily  separated  with  needles  (teasing).  Such  specimens 
are  usually  best  examined  when  mounted  on  a  slide  in  some  of  the 
macerating-fluid.  Many  of  the  macerating-solutions  not  only  favor 
the  separation  of  the  constituents  of  tissues,  but  also  preserve  them, 
so  that  a  fair  idea  of  their  natural  size  and  shape  may  be  obtained 
from  such  preparations.  It  is  evident,  however,  that  with  this 
method  very  little  can  be  learned  of  their  arrangement  in  the  tis- 
sues before  they  were  separated,  and  a  knowledge  of  that  arrange- 
ment is  often  of  greater  importance  in  the  determination  of  the 
character  of  the  tissue  than  a  knowledge  of  the  exact  shape  and 
size  of  the  tissue-elements. 

The  third  method,  that  of  preparing  sections  of  the  tissues,  is  the 
one  most  commonly  employed,  because  it  yields  the  most  useful 
results.  The  structural  elements  composing  the  tissues  are  seen  in 
their  natural  relative  positions,  and  can  be  distinguished  from  each 
other  and  identified  by  the  use  of  dyes  and  other  reagents  that 
affect  them  in  some  characteristic  manner.  But  in  order  to  ob- 
tain useful  sections  the  tissues  must  almost  always  undergo  some 
preliminary  treatment  with  reagents,  to  give  them  a  proper  consist- 
ency for  cutting  and  to  hold  the  tissue-elements  together  so  that 
the  sections  shall  not  fall  apart  after  they  have  been  cut.  This  may 
be  accomplished  by  freezing  the  tissue  before  cutting  it ;  but  more 
satisfactory  results  are  obtained  by  causing  a  coagulation  of  the 
albuminous  substances  and  subsequently  extracting  some  or  all  of 
the  water  contained  in  the  tissues.  These  changes  in  the  tissues 
give  them  a  firmness  which  favors  the  preparation  of  very  thin  sec- 
tions ;  but  sometimes  even  they  are  inadequate,  and  then  the  tissues 
are  usually  impregnated  with  some  substance,  like  paraffin  or  col- 
lodion, which  fills  the  interstices  of  the  tissues  and  can  then  be 
hardened,  when  it  serves  to  hold  the  tissue-elements  together  and 
retain  them  in  their  natural  positions.  The  paraffin  or  hardened 
collodion  is  cut  with  the  tissues  and  keeps  the  sections  from  disinte- 
grating. Before  mounting  the  section,  the  substance  used  for  im- 
pregnation may  be  removed  from  the  section,  or  it  may  be  retained 


MICROSCOPICAL   TECHNIQUE.  401 

* 

permanently,  since  it  is  usually  easily  recognized  in  the  specimen 
and  does  not  interfere  with  its  study  under  the  microscope. 

The  study  of  tissues  by  means  of  sections  has  the  disadvantage 
that  the  elements  of  the  tissues  are  cut,  and  the  sections  contain  the 
resulting  portions  as  well  as  complete  elements.  The  incomplete 
portions  lie  near  and  at  the  surfaces  of  the  sections,  where  they  are 
in  clearest  view,  while  the  uncut  elements  are  situated  in  the  body 
of  the  section,  more  or  less  obscured  by  the  overlying  portions  that 
have  been  cut  by  the  knife.  Moreover,  the  tissue-elements  may  lie 
obliquely  to  the  plane  of  the  section,  so  that  only  a  portion  of  them 
can  be  seen  at  a  time,  the  rest  being  brought  into  clear  view  only 
when  the  foc^l  plane  is  raised  or  lowered.  These  circumstances  and 
the  fact  that  the  tissue-elements  are  frequently  closely  crowded 
together  make  the  interpretation  of  sections  a  matter  of  some  dif- 
ficulty in  many  cases.  These  difficulties  are  in  a  measure  overcome 
by  examining  sections  of  different  thicknesses,  but  a  more  satis- 
factory way  of  studying  the  structure  of  a  tissue  is  to  examine  por- 
tions after  maceration  as  well  as  in  section. 

The  processes  of  coagulation  and  dehydration,  which  have  already 
been  mentioned  as  usual  preliminaries  to  the  cutting  of  sections, 
deserve  a  few  words  in  explanation  of  their  purposes. 

The  coagulation  of  the  albuminous  substances  in  the  tissues  has 
for  its  chief  aim  the  preservation  of  the  minute  structure  of  the 
tissue-elements,  so  that  a  lapse  of  time  or  the  subsequent  manipula- 
tions of  the  tissues  shall  not  cause  an  alteration  in  the  details  which 
it  is  desired  to  study.  If  this  precaution  be  omitted,  the  tissues 
undergo  post-mortem  changes  which  seriously  alter  the  appear- 
ance of  the  elements  of  which  they  are  composed.  Coagulation 
brought  about  for  this  purpose  is  called  "  fixation  "  of  the  tissues. 
It  may  be  induced  in  a  variety  of  ways :  the  tissues  may  be  sub- 
jected to  heat  for  a  few  moments,  thus  rendering  the  albumins  they 
contain  both  solid  and  insoluble ;  but  the  more  usual  procedure  is 
to  immerse  the  tissues  in  a  solution  of  some  substance  that  causes 
rapid  death  with  coagulation.  These  solutions  are  called  fixing- 
solutions,  and  not  infrequently  the  substances  they  contain  not  only 
cause  death  and  coagulation,  but  also  form  a  union  with  some  of 
the  structural  materials  of  the  tissues  which  may  facilitate  their 
subsequent  recognition. 

The  number  of  formulae  that  have  been  devised  for  the  prepara- 
tion of  fixing-solutions  is  very  great,  and  some  of  the  solutions  are 

26 


402  HISTOLOGICAL  TECHNIQUE. 

better  for  the  fixation  of  some  tissues  than  for  others.  As  a  rule, 
those  solutions  that  most  perfectly  preserve  the  finer  intracellular 
details  of  structure  have  very  little  power  of  penetrating  masses 
of  tissue.  They  can,  therefore,  only  be  employed  when  very  small 
bits  of  tissue  are  to  be  fixed.  Other  fixing-solutions  penetrate 
much  better,  but  fail  to  fix  the  most  delicate  structures,  which  may 
undergo  changes  before  they  are  preserved.  It  follows  that  the 
choice  of  the  method  of  fixation  must  in  each  case  depend  upon 
the  object  to  be  attained. 

The  removal  of  water  from  the  fixed  tissues  is  accomplished  by 
means  of  alcohol.  The  fixing-agents  are  nearly  all  aqueous  solu- 
tions, and  while  they  increase  the  consistency  of  the  tissues  to  a 
certain  extent,  they  do  not  usually  render  them  sufficiently  firm  for 
the  preparation  of  thin  and  uniform  sections.  If  the  water  in  the 
tissues  be  replaced  by  alcohol,  a  greater  and  more  uniform  con- 
sistency is  obtained,  and  the  tissues  are  also  partly  prepared  for 
impregnation  with  an  embedding-material  (collodion  or  paraffin) 
should  that  be  necessary  for  section-cutting. 

After  sections  of  fixed  tissues  have  been  obtained  they  usually 
require  staining  before  they  can  be  profitably  studied.  The  chief 
reason  for  this  will  appear  in  the  following  explanation  : 

When  a  specimen  is  examined  under  the  microscope  differences 
in  structure  among  the  colorless  elements  of  the  specimen  may  be 
seen,  or  differences  in  color  between  the  different  elements  may  be 
perceptible.  We  may,  then,  distinguish  between  a  "  structure- 
picture/'  due  to  differences  that  are  not  those  of  color,  and  a  "  color- 
picture,"  due  solely  to  such  differences.  The  manner  in  Avhich  the 
latter  is  produced  is,  perhaps,  self-evident.  The  structure-picture 
is  the  result  mainly  of  differences  in  refraction  due  to  the  various 
densities  of  different  parts  of  the  specimen.  But  the  processes  of 
fixation  and  hardening  have  for  their  purpose  the  rendering  of  the 
tissues  of  a  relatively  uniform  density.  They  must,  in  consequence, 
tend  to  obliterate  the  details  of  the  structure-picture  which  the 
sections  yield  when  viewed  under  the  microscope.  For  this  reason 
the  sections  are  stained,  which  converts  the  structure-picture  into  a 
color-picture. 

The  substances  composing  the  tissues  have  various  affinities  for 
dyes,  and  it  is  possible  to  take  advantage  of  this  in  staining  sec- 
tions, so  that  structures  of  the  same  nature  shall  receive  one  color, 
while  those  of  different  composition  shall  be  dyed  of  a  different 


MKTIIODS  OF  FIXATION.  403 

line  or  an  entirely  different  color.  The  coloring-matters,  when  so 
employed,  not  only  bring  out  the  structure  of  the  tissue  by  creating 
a  color-picture,  but  they  also  serve  as  valuable  reagents  in  revealing 
the  nature  of  the  substances  to  which  they  impart  a  color.  Again, 
it  is  often  necessary  that  a  certain  method  of  fixation  or  other  pre- 
liminary treatment  should  be  used  before  the  particular  dye  selected 
can  display  its  greatest  selective  power  for  a  particular  substance. 
These  facts  explain  the  great  number  of  formulae  for  stains  and  the 
preparation  of  specimens  that  are  found  in  the  technical  text-books 
and  journals.  The  subject  has  become  so  expanded  within  recent 
years  that  it  has  almost  created  a  distinct  branch  of  learning ;  but 
it  will  only  be  necessary  for  the  student  of  medicine  to  acquire  a 
knowledge  of  a  few  methods  that  will  serve  to  reveal  the  general 
structure  of  cells  and  the  characters  of  the  intercellular  substances. 
The  general  outline  of  the  procedures  in  common  use  for  this  pur- 
pose are  as  follows :  1,  fixation ;  2,  hardening ;  3,  impregnation ; 
4,  embedding  ;  5,  cutting ;  6,  staining ;  7,  dehydration  ;  8,  clearing  ; 
9,  mounting. 

Some  methods  of  preparation  combine  one  or  more  of  these  steps 
in  a  single  manipulation,  thus  considerably  reducing  the  time  requi- 
site for  the  completion  of  the  process.  Other  methods  necessitate 
the  intercalation  of  still  other  manipulations,  or  the  subdivision 
of  those  already  enumerated. 

Methods  of  Fixation. 

1.  Mliller's  Fluid. — This  classic  fixing-  and  hardening-solution  con- 
sists of  potassium  bichromate,  2.5  per  cent.,  and  sodium  sulphate, 
1  per  cent.,  dissolved  in  water  (preferably  distilled  water).  It  is 
slow  in  action,  requiring  from  six  to  eight  weeks  for  the  preservation 
of  an  average  specimen,  but  with  proper  care  can  be  made  to  yield 
excellent  results  when  the  finer  details  of  structure  are  not  to  be 
studied.  It  is  important  to  use  large  quantities  of  the  fluid,  at 
least  ten  times  the  volume  of  the  tissues  immersed  in  it,  and  to 
renew  the  fluid  so  frequently  that  its  strength  shall  be  constantly 
maintained.  When  fresh  tissues  are  placed  in  Miiller's  fluid  they 
speedily  render  it  cloudy.  This  is  a  sign  that  the  fluid  should  be 
renewed,  even  if  only  an  hour  has  elapsed  since  the  tissues  were 
placed  in  it.  When  cloudiness  no  longer  appears  the  fluid  should 
be  renewed  once  a  day  for  the  first  two  weeks  :  after  that,  two  or 
three  times  a  week  till  the  process  is  completed. 


404  HISTOLOGICAL   TECHNIQUE. 

After  fixation  in  Miiller's  fluid  specimens  should  be  washed  in 
running  water  over  night,  or  for  twenty-four  hours,  and  then  hard- 
ened in  alcohols  of  progressively  greater  strengths.  While  in  the 
weaker  alcohols  specimens  should  be  kept  in  the  dark,  to  avoid 
the  formation  of  precipitates,  which  occur  under  the  influence  of 
light.  Pieces  of  tissue  placed  in  Miiller's  fluid  should  not  be  more 
than  1  cm.  in  thickness. 

Two  excellent  modifications  of  Miiller's  fluid  have  been  devised 
by  Zenker  and  Orth  for  the  purpose  of  hastening  the  fixation  and 
of  securing  a  more  faithful  preservation  of  structural  detail. 

2.  Zenker's  Fluid. — 

Potassium  bichromate,  2.5  grams. 

Sodium  sulphate,  1      gram. 

Mercuric  chloride,  5     grams. 

Distilled  water,  100     cc. 

To  this  stock  solution  5  per  cent,  of  glacial  acetic  acid  is  to  be 
added  just  before  use  of  the  fluid. 

Zenker's  fluid  fixes  tissues  in  from  three  to  twenty-four  hours. 
The  pieces  should  not  be  more  than  5  mm.  thick,  and  after  fixa- 
tion should  be  washed  for  several  hours  in  running  water  and  then 
hardened  in  alcohol. 

This  solution  possesses  the  disadvantage  that  a  precipitation  of 
mercury  or  some  mercurial  compound  is  likely  to  take  place  within 
the  tissues.  This  deposit  may  be,  at  least  in  great  measure,  removed 
from  the  tissues  by  adding  a  little  tincture  of  iodine  to  the  harden- 
ing-alcohols.  The  iodine  combines  with  the  mercury  and  produces 
a  soluble  compound,  which  is  dissolved  out  by  the  alcohol.  As  the 
iodine  disappears  from  the  alcohol  the  latter  becomes  bleached,  and 
fresh  tincture  must  be  added  until  the  alcohol  remains  permanently 
tinged.  If,  after  sections  of  the  tissue  have  been  prepared,  they 
are  found  to  contain  a  mercurial  deposit,  this  can  be  removed  by 
treatment  with  dilute  iodine  tincture  or  with  LugoFs  solution. 

3.  Orth's  Fluid.— 

Potassium  bichromate,  2.5  grams. 

Sodium  sulphate,  1     gram. 

Distilled  water,  100     cc. 

This  stock  solution  is  Muller's  fluid.     Before  use,  10  cc.  of  for- 


METHODS  OF  FIXATION.  405 

maldehyde  (40  per  cent.)  is  to  be  added  to  every  100  cc.  of  the 
Miiller's  fluid. 

Orth's  fluid  fixes  in  three  or  four  days.  The  pieces  of  tissue 
should  not  be  more  than  1  cm.  thick.  The  time  for  fixation  can 
be  shortened  if  smaller  pieces  are  used  and  the  process  is  carried 
on  at  a  slightly  elevated  temperature ;  e.  g.,  in  an  incubator  kept  at 
37°  C.  (98.6°  F.).  After  fixation  the  specimens  should  be  washed 
in  running  water,  as  in  the  previous  methods. 

4.  Mercuric  Chloride  Solution. — A  saturated  solution  of  corrosive 
sublimate  in  0.5  per  cent,  salt  solution  is  prepared  by  heating  an 
excess  of  sublimate  crystals  in  the  salt  solution  and  allowing  the 
mixture  to  cool.     The  clear  fluid  is  decanted  from  the  crystals  when 
desired  for  use.     The  penetration  and  action  of  the  solution  are 
favored  by  the  addition  of  5  per  cent,  of  glacial  acetic  acid  at  the 
time  of  using.     The  thickness  of  the  pieces  of  tissue  should  not 
exceed  5  mm.,  and  much  thinner  pieces  are  better.     Fixation  takes 
place  within  six  hours,  after  which  the  tissues  may  be  washed  in 
running  water,  or  placed  at  once  in  70  per  cent,  alcohol.     If  acetic 
acid  has  been  used,  it  is  best  to  wash  in  water  before  immersing  in 
alcohol.     Tincture  of  iodine  should  be  added  to  the  alcohol  for  the 
reasons  given  in  the  description  of  Zenker's  fluid. 

5.  Formaldehyde. — This  gas    is   capable    of   being  absorbed   by 
water  to  form  a  40  per  cent,  solution,  but  its  volatility  renders  such 
a  solution  liable  to  deterioration.     The  strength  employed  for  fixa- 
tion is  usually  4  per  cent.,  and  may  be  prepared  by  adding  10  cc. 
of  40  per  cent,  formaldehyde  to  90  cc.  of  distilled  water.     A  0.75 
per  cent,  solution  of  common  salt  may  be  substituted  for  the  distilled 
water  with  possible  advantage. 

Formaldehyde  penetrates  deeply  and  quickly  into  the  tissues, 
which  may  be  1  cm.  in  thickness,  and  accomplishes  fixation  within 
twenty-four  hours,  but  the  preservation  of  structural  detail  is  not 
very  perfect.  The  solution  is  useful  where  the  general  characters 
of  the  tissues  are  to  be  determined  and  the  details  of  the  cells  are 
of  comparatively  little  consequence.  After  fixation  the  tissues  may 
be  washed  in  water,  or  placed  directly  in  70  per  cent,  alcohol ;  or 
frozen  sections  may  be  at  once  prepared.  Satisfactory  sections  may 
be  obtained  from  small  pieces  of  tissue  if  they  are  put  in  the  for- 
maldehyde solution  for  an  hour  or  two  and  then  cut  with  the 
freezing-microtome.  After  they  have  been  washed  for  a  short  time 
in  water  they  may  be  stained  by  any  of  the  more  usual  methods. 


406  HISTOLOGICAL   TECHNIQUE. 

6.  Flemming's  Solution. — This  is  a  solution  containing  osmic  acid, 
chromic  acid,  and  acetic  acid.  It  does  not  keep  well,  and  it  is  best 
to  prepare  it  just  before  it  is  to  be  used.  For  this  purpose  the 
following  stock  solutions  may  be  kept  on  hand : 

A.  2  per  cent,  solution  of  osmic  acid  in  1  per  cent,  chromic  acid. 

B.  1  per  cent,  solution  of  chromic  acid  in  distilled  water. 
Osmic  acid  is  sold  in  sealed  tubes  containing  1  gram.    To  prepare 

the  stock  solution  "  A,"  the  tube  should  be  washed  on  the  outside 
and  a  deep  file-scratch  made  near  its  centre.  It  should  then  be 
broken  into  a  bottle  containing  50  cc.  of  a  1  per  cent,  solution  of 
chromic  acid  in  distilled  water.  The  halves  of  the  tube  should  be 
dropped  into  the  bottle  and  its  contents  shaken  at  intervals  until 
solution  is  effected.  This  solution  had  best  be  kept  in  the  dark 
to  avoid  decomposition  of  the  osmic  acid.  When  required  for  use, 
prepare  the  Flemming's  solution  by  mixing : 

Solution  "  A,"  4  cc. 

Solution  "B,"  15   " 

Glacial  acetic  acid,  1   " 

Flemming's  solution  is  especially  useful  for  fixing  the  finer  details 
of  structure  within  the  cell.  It  was  devised  for  the  preservation 
of  the  mitotic  figures  formed  during  karyokinesis,  but  its  range  of 
usefulness  far  exceeds  that  limited  application.  Its  power  of  pene- 
tration is  very  slight  and  the  pieces  of  tissue  selected  for  fixation 
must  be  small.  They  should  not  exceed  2  mm.  in  their  least 
measurement,  and  thinner  pieces  are  apt  to  give  better  results. 
Owing  to  the  presence  of  osmic  acid,  Flemming's  solution  stains 
fat  a  dark-brown  or  black  color,  and  may  be  used  as  a  reagent  for 
the  identification  of  fatty  substances. 

Tissues  should  be  left  in  Flemming's  solution  for  about  twenty- 
four  hours,  though  twice  that  length  of  time  would  cause  little  if 
any  harm.  They  must  then  be  thoroughly  washed  in  running  water 
for  twenty-four  hours  or  longer,  and  hardened  in  alcohol.  Since 
Flemming's  solution  is  usually  employed  for  the  study  of  the 
individual  cells,  it  is  desirable  to  prepare  very  thin  sections  of  the 
tissues  that  have  been  hardened  in  it.  For  this  purpose  embedding 
in  paraffin  is  the  best  method. 

The  foregoing  fixing  solutions  will  meet  most  of  the  requirements 
of  the  practitioner  of  medicine,  but  it  frequently  happens  that  he 


METHODS  OF  FIXATION.  407 

would  like  to  obtain  speedy  results  from  a  microscopical  examina- 
tion without  running  the  risk  of  loss  of  material  or  of  poor  results. 
When  this  is  the  case  he  may  use  absolute  alcohol  as  a  fixing-agent, 
thus  taking  advantage  also  of  its  ability  to  harden  tissues  and  fit 
them  for  rapid  embedding  in  collodion. 

7.  Absolute  Alcohol. — If  fresh  tissues  are  placed  in  strong  alcohol, 
say  95  per  cent.,  they  are  hardened ;  but  during  the  process  there 
is  an  opportunity  for  the  albuminous  fluids  in  the  tissues  to  escape 
to  a  certain  extent,  and  for  shrinkage  to  take  place  in  consequence. 
If  absolute  alcohol  be  employed,  it  causes  such  rapid  coagulation 
that  this  leaching  of  the  tissues  does  not  take  place.  It  is  neces- 
sary, however,  that  the  alcohol  should  remain  of  nearly  its  original 
strength,  otherwise  the  water  in  the  tissues  will  dilute  it  sufficiently 
to  destroy  this  coagulating  action. 

An  excellent  means  for  maintaining  the  strength  of  the  alcohol 
is  to  immerse  in  it  a  few  lumps  of  quick-lime.  Take  a  small 
jar  that  can  be  hermetically  closed  by  a  tightly  fitting  cover 
(a  museum  jar,  holding  six  or  eight  ounces,  will  answer).  Place 
the  lime  in  the  bottom  and  then  nearly  fill  with  absolute  alcohol. 
A  few  pieces  of  crumpled  filter-paper  are  placed  upon  the  lime  and 
covered  with  a  smooth  piece  placed  so  as  to  slant  a  little.  The 
latter  should  lie  near  the  surface  of  the  alcohol,  but  be  entirely  sub- 
merged. Small  pieces  of  the  tissue  to  be  fixed  are  placed  upon  the 
filter-paper  where  they  will  be  covered  by  the  alcohol.  The  alco- 
hol immediately  coagulates  the  albuminous  substances  on  the  sur- 
face of  the  pieces  and  then  gradually  replaces  the  water  in  the 
specimen,  coagulating  the  deeper-seated  albumins  as  it  penetrates 
the  mass.  The  expelled  water  sinks  to  the  bottom  of  the  jar,  owing 
to  its  greater  specific  gravity,  and  is  at  once  taken  up  by  the  lime. 
It  is  essential  for  the  success  of  this  method  that  the  lime  should 
be  exceedingly  quick.  It  must  show  immediate  signs  of  slaking 
if  even  a  drop  of  water  be  placed  upon  it.1 

It  will  be  seen  that  this  method  not  only  fixes  the  tissues,  but 
quickly  dehydrates  them.  The  real  dehyd rating-agent  is,  however, 
the  lime,  the  alcohol  serving  merely  as  a  vehicle  for  conveying  the 
water  from  the  specimen  to  the  lime.  If  the  pieces  of  tissue  are 

1  A  jar  of  absolute  alcohol,  prepared  as  above,  may  be  used  for  purposes  of  fix- 
ing or  hardening  until  the  lime  has  become  slaked  or  the  alcohol  so  impregnated 
with  dissolved  fat  that  the  latter  interferes  with  embedding  in  collodion.  When  the 
latter  is  the  case  the  hardened  collodion  is  opaque  or  opalescent. 


408  HISTOLOGICAL  TECHNIQUE. 

small,  not  over  5  mm.  thick,  they  will  be  hardened  by  remaining 
in  the  absolute  alcohol  over  night,  and  mounted  sections  may  be 
ready  for  examination  by  the  next  afternoon. 

8.  Fixation  by  Boiling. — Throw  small  pieces  of  the  tissue,  not 
larger  than  1  cm.,  into  boiling  0.75  per  cent,  salt  solution.  Keep 
them  at  the  temperature  of  boiling  for  two  minutes.  Then  throw 
them  into  cold  water.  They  may  then  be  cut  with  the  freezing- 
microtome,  or  may  be  placed  in  70  per  cent,  alcohol  for  hardening. 
This  method  is  excellent  for  the  detection  of  albuminous  exudates 
within  the  tissues,  but  it  causes  so  much  shrinkage  that  it  is  not 
useful  for  general  purposes. 

Methods  of  Hardening. 

Solutions  of  chromates,  as  Miiller's  fluid,  will,  after  a  time,  con- 
fer a  pretty  firm  consistency  upon  tissues,  and  even  render  them 
brittle.  Tissues  fixed  in  corrosive  sublimate  are  also  very  much 
hardened.  But  the  usual  practice  is  to  harden  specimens  in  alcohol 
after  fixation.  To  obtain  the  best  results  this  hardening  should  be 
done  gradually,  since  immersion  in  strong  alcohol  is  apt  to  produce 
undesirable  shrinkage,  affecting  the  various  tissue-elements  in  dif- 
ferent degree. 

Seventy  per  cent,  alcohol  (736  cc.  95  per  cent,  alcohol  to  264  cc. 
water)  is  weak  enough  to  begin  with.  After  the  tissues  have  been  in 
alcohol  of  that  strength  for  twenty-four  to  forty-eight  hours,  accord- 
ing to  the  size  of  the  pieces,  they  are  placed  in  80  per  cent,  alcohol 
(842  cc.  95  per  cent,  alcohol  to  158  cc.  water)  for  an  equal  length 
of  time,  and  then  in  95  per  cent,  alcohol.  From  the  95  per  cent, 
alcohol  they  are  placed  in  absolute  alcohol,  if  it  be  desired  to  embed 
them  in  either  collodion  or  paraffin.  If  they  are  not  intended  for 
immediate  use,  they  may  be  kept  indefinitely  in  80  per  cent,  alcohol. 

During  the  hardening  it  is  best  not  to  allow  the  tissues  to  rest 
on  the  bottom  of  the  vessel  containing  the  alcohol,  as  they  are 
liable  to  slight  maceration  in  the  alcohol,  which  there  becomes 
diluted  with  water  from  the  specimen.  They  can  be  kept  off 
the  bottom  by  means  of  a  little  crumpled  filter-paper.  Specimens 
that  have  been  fixed  in  a  chromate  solution  should  be  kept  in  the 
dark  while  being  hardened ;  those  that  have  been  fixed  in  corrosive 
sublimate  should  be  hardened  in  alcohols  to  which  a  little  tincture  of 
iodine  (sufficient  to  give  them  a  sherry  color)  has  been  added.  When 
absolute  alcohol  is  used,  its  strength  should  be  maintained  by  con- 


METHODS  OF  IMPREGNATION.  409 

tact  with   quick-lime  (see  directions  for  fixing  tissues  in  absolute 

alcohol). 

Methods  of  Impregnation. 

When  tissues  are  so  porous  or  friable  that  sections  are  likely  to 
tear  or  -disintegrate  it  is  desirable  to  impregnate  them  with  some 
embedding-material.  The  most  useful  substances  for  this  purpose 
are  collodion,  or  celloidin,  and  paraffin.  Whichever  of  these  is 
used,  it  is  necessary  to  remove  the  water  from  the  specimen  before 
the  impregnation  can  be  accomplished,  for  both  collodion  and 
paraffin  are  insoluble  in  water.  Tissues  that  have  been  hardened 
in  alcohol  are  to  a  certain  extent  already  dehydrated.  The  residual 
water  may  be  removed  or  reduced  to  a  trace  by  treatment  with 
absolute  alcohol,  in  which  collodion  is  soluble. 

The  "  celloidin  "  manufactured  by  Schering  is  an  excellent  prep- 
aration of  gun-cotton,  but  almost  equally  good  results  may  be 
obtained  by  using  the  more  economical  soluble  cottons  employed  by 
photographers.  Two  solutions  in  a  mixture  of  equal  volumes  of 
ether  and  absolute  alcohol  (both,  if  possible,  of  Squibb's  prepara- 
tion) should  be  kept  in  stock  :  one,  a  weaker  solution,  having  about 
the  consistency  of  thin  mucilage ;  the  other,  a  stronger  solution, 
resembling  a  syrup. 

Collodion  is  soluble  in  absolute  alcohol,  so  that  tissues  containing 
only  that  fluid  are  ready  for  impregnation  without  further  prelim- 
inary treatment.  When  thorough  impregnation  is  desired  the  tissues 
should  be  immersed  in  equal  parts  of  ether  and  absolute  alcohol  for 
a  few  days,  and  then  in  the  weaker  solution  of  celloidin  or  collodion 
for  a  number  of  days  or  weeks — the  longer  the  better;1  but  such 
complete  impregnation  is  often  unnecessary,  and  soaking  for  a  day 
or  two  will  often  suffice  if  the  sections  to  be  made  need  not  be  very 
thin.  It  is  not  possible,  in  any  event,  to  make  very  thin  sections 
from  tissues  embedded  in  collodion  ;  but  sections  of  large  area  may 
be  obtained,  which  is  often  of  greater  importance.  For  very  thin 
sections  it  is  better  to  use  paraffin  for  the  embedding-material, 
although  the  resulting  sections  will  have  to  be  smaller. 

Paraffin  is  insoluble  in  alcohol  of  all  strengths.  It  is  therefore 
necessary  to  remove  the  absolute  alcohol  from  the  tissues  before 
they  can  be  impregnated  with  paraffin.  This  may  be  done  by 
immersing  the  tissues  in  some  liquid  that  is  a  solvent  for  paraffin 

1  Impregnation  may  be  greatly  hastened  if  done  at  the  body-temperature  in  a 
hermetically  closed  vessel. 


410  HISTOLOGICAL  TECHNIQUE. 

and  is  also  miscible  with  alcohol.  For  this  purpose,  xylol,  chloro- 
form, or  oil  of  cedar-wood  may  be  used.  Xylol  yields  the  most 
rapid  results,  but  its  use  is  contraindicated  when  it  is  desired  to 
retain  fatty  substances  that  have  been  colored  with  osmic  acid,  as 
the  xylol  extracts  them.  If  their  preservation  within  the  tissues 
is  important,  chloroform  should  be  used ;  but  the  sojourn  even  in 
that  liquid  should  be  as  short  as  possible.  Oil  of  cedar-wood  prob- 
ably causes  less  change  in  tissues  than  chloroform,  but  the  method 
is  more  protracted,  and,  requiring  longer  treatment  in  the  paraffin- 
oven,  probably  has  little  ultimate  advantage  over  chloroform  for 
general  purposes. 

If  xylol  is  used,  the  tissues  are  transferred  from  the  absolute 
alcohol  to  xylol,  on  which  they  at  first  float,  Subsequently  they 
sink,  and  are  gradually  rendered  transparent  as  the  alcohol  is 
expelled  by  the  xylol.  When  there  are  no  opacities  left  the  speci- 
men is  ready  for  the  paraffin-oven.  These  changes  take  from  two 
to  twenty-four  hours. 

The  treatment  with  chloroform  is  similar  to  that  with  xylol,  but 
after  the  tissues  have  been  cleared  in  chloroform  (six  to  twenty-four 
hours)  they  are  immersed  in  a  saturated  solution  of  paraffin  in 
chloroform  for  about  the  same  length  of  time.  They  are  then  ready 
for  the  paraffin-oven. 

When  oil  of  cedar-wood  is  used  the  pieces  should  be  soaked  in 
two  successive  portions  of  the  oil,  about  twelve  hours  in  each,  to 
insure  removal  of  the  alcohol. 

The  foregoing  steps  are  all  preliminary  to  the  actual  impregnation 
with  paraffin. 

It  is  important  that  the  paraffin  used  for  impregnation  and 
embedding  should  have  a  wax-like,  and  not  a  crystalline,  texture, 
and  that  its  melting-point  should  be  such  that  its  consistency  will 
be  favorable  for  cutting  at  the  average  temperature  of  the  labora- 
tory. Griibler,  of  Leipzig,  furnishes  excellent  qualities  of  paraffin. 
For  a  room-temperature  of  20°  C.  (68°  Fah.)  a  variety  melting  at 
50°  C.  (122°  Fah.)  will  give  good  results.  If  the  laboratory  is 
warmer,  a  paraffin  of  higher  melting-point  should  be  used. 

Impregnation  is  accomplished  by  placing  the  bits  of  tissue  in  a 
bath  of  melted  paraffin  maintained  at  a  temperature  only  slightly 
above  that  of  fusion,  say  52°  C.  (125.6°  Fah.),  if  the  paraffin  melts 
at  50°  C.  (122°  Fah.).  This  may  be  accomplished  in  a  water- 
jacketed  oven  provided  with  a  thermoregulator,  or  upon  a  plate  of 


METHODS  OF  EMBEDDING.  411 

brass  or  copper,  resting  on  a  tripod  and  heated  at  one  end  by  a 
burner.  When  the  latter  method  is  employed  the  paraffin  is  melted 
in  a  little  glass  dish,  which  is  moved  along  the  plate  until  a  point 
is  found  at  which  the  paraffin  remains  melted  at  the  bottom,  but  is 
covered  at  the  edges  of  the  surface  with  a  thin  layer  of  congealed 
paraffin. 

The  length  of  time  that  the  specimens  should  remain  in  the 
melted  paraffin  will  vary  with  the  character  of  the  tissues  and  the 
method  of  getting  rid  of  the  alcohol  which  has  been  employed.  It 
should  not  be  protracted  longer  than  necessary  for  complete  impreg- 
nation, as  heat  is  injurious  to  the  tissues.  When  xylol  has  been 
used  two  hours  will  usually  suffice  if  the  pieces  of  tissue  are  small, 
and  especially  if  they  are  transferred  to  a  fresh  paraffin-bath  after 
about  an  hour.  This  renewal  of  the  paraffin  is  still  more  important 
if  oil  of  cedar-wood  has  been  used.  Chloroform  requires  a  little 
more  time  than  xylol,  and  should  be  transferred  to  fresh  paraffin 
once  or  twice. 

When  impregnation  has  taken  place  and  the  final  bath  of  paraffin 
no  longer  has  the  slightest  odor  of  the  clearing-agent  the  pieces  of 
tissue  are  removed  from  the  bath  with  warmed  forceps  and  placed 
on  bits  of  writing-paper,  to  which  they  adhere.  A  designation 
of  the  specimen  may  be  written  on  these  papers,  and  the  tissues 
kept  in  this  condition  until  required  for  cutting.  They  must  then 
be  embedded. 

Methods  of  Embedding. 

The  object  of  embedding  is  to  surround  the  piece  of  tissue  from 
which  sections  are  to  be  cut  with  a  mass  of  the  embedding-sub- 
stance,  which  then  not  only  supports  the  tissue  when  it  comes  in 
contact  with  the  knife,  but  also  affixes  it  to  a  block  or  other  support 
which  can  be  fitted  into  the  clamp  of  the  microtome. 

Microtomes  designed  for  cutting  paraffin  usually  have  special 
supports  for  the  embedded  specimen,  but  blocks  of  hard  wood  may 
be  used  in  their  place. 

For  the  support  of  tissues  embedded  in  collodion  blocks  of  plate- 
glass  are  probably  both  better  and  cheaper  than  those  made  of  other 
materials.  They  may  be  easily  prepared  from  waste  pieces  of  plate- 
glass,  about  a  quarter  of  an  inch  thick,  and  "  obscured  "  or  ground  on 
one  surface.  The  glass  may  be  cut  into  blocks  of  any  desired  size  by 
scoring  the  smooth  side  with  a  diamond  and  then  splitting  the  pieces 
apart  with  a  sharp  blow  from  a  wedge-shaped  hammer.  The  em- 


412  HISTOLOGICAL  TECHNIQUE. 

bedded  specimen  is  affixed  to  the  rough  surface  of  these  blocks  by 
means  of  collodion,  and  the  blocks  may  be  numbered  with  a  lead 
pencil  upon  the  rough  surface.  The  writing  will  be  preserved  from 
obliteration  by  the  specimen  subsequently  placed  upon  it,  and  can 
be  read  through  the  glass. 

1.  Embedding  in  Collodion  (or  Celloidin). — Tissues  of  firm  con- 
sistency and  moderately  uniform  structure,  such  as  liver,  kid- 
ney, and  the  majority  of  tumors  which  have  been  hardened, 
may  be  embedded  without  previous  impregnation.  Before  this 
can  be  done,  however,  they  must  be  either  dehydrated  with  abso- 
lute alcohol,  or  soaked  for  a  few  hours  in  a  mixture  of  equal 
volumes  of  ether  and  alcohol  (95  per  cent,  alcohol  will  answer, 
if  absolute  alcohol  is  not  to  be  had).  For  this  rapid  method  the 
bottom  of  the  piece  of  tissue  must  be  flat  and  parallel  to  the  plane  of 
the  desired  sections.  When  the  necessary  trimming  of  the  speci- 
men is  completed  moisten  it  with  absolute  alcohol  or  the  ether- 
alcohol  mixture,  then  dip  it  in  the  thick  solution  of  gun-cotton  and 
place  it  at  once  upon  the  ground  surface  of  the  glass  block  (pre- 
viously labelled).  In  a  few  minutes  the  collodion  will  have  evap- 
orated sufficiently  for  the  formation  of  a  distinct  pellicle  upon  its 
surface.  When  this  has  become  firm  enough  to  withstand  gentle 
pressure  immerse  the  block  and  specimen  in  several  times  their  vol- 
ume of  80  per  cent,  alcohol.  This  will  harden  the  collodion,  and  in 
the  course  of  a  few  hours  the  specimen  will  be  ready  for  cutting. 

Tissues  impregnated  with  collodion  had  best  be  embedded  by  a 
slower  process  than  the  foregoing,  although  that  method  will  answer 
where  only  a  slight  support  of  the  tissue-elements  within  the  speci- 
men is  needed.  A  gradual  concentration  of  the  collodion  within 
the  tissues  may  be  brought  about  in  the  following  manner : 

Smear  the  inside  of  a  small,  straight-sided  glass  dish  with  a  trace 
of  glycerin  and  then  fill  it  with  enough  moderately  thick  collodion 
to  cover  the  pieces  of  tissue  with  a  layer  about  one-quarter  of  an 
inch  deep.  Now  place  the  specimens  that  have  been  in  thin  collo- 
dion in  the  dish,  with  the  surfaces  from  which  sections  are  to  be  cut 
resting  on  the  bottom.  Place  the  dish  in  a  larger  vessel  with  higher 
sides  and  loosely  cover  the  latter.  The  ether  and  alcohol  in  the 
collodion  will  gradually  evaporate,  and  their  vapors  will  first  fill  the 
outer  vessel  and  then  overflow  its  sides.  The  depth  of  the  outer 
vessel  keeps  these  vapors  in  contact  with  the  surface  of  the  collo- 
dion, preventing  the  formation  of  a  pellicle,  which  would  retard 


METHODS  OF  EMBEDDING.  413 

evaporation  and  also  favor  the  formation  of  bubbles  in  the  collo- 
dion. After  an  interval  of  one  or  more  days  the  collodion  will  have 
a  gelatinous  consistency.  It  should  be  allowed  to  become  so  hard 
that  it  has  considerable  firmness,  but  is  still  soft  enough  to  receive 
an  impression  of  the  ridges  in  the  skin  when  pressed  with  the 
finger.  The  outer  vessel  is  then  partly  filled  with  80  per  cent, 
alcohol  so  that  the  whole  of  the  inner  dish  is  submerged. 

By  the  next  day  the  collodion  will  be  hard  enough  for  removal 
from  the  dish.  With  a  small  scalpel,  held  vertically,  divide  the 
hardened  mass  of  collodion  into  portions,  each  of  which  contains 
one  of  the  pieces  of  tissue  (for  several  pieces  may  be  embedded  in 
the  same  dish,  provided  care  be  taken  to  preserve  their  identity). 
Remove  the  pieces  and  trim  down  the  collodion  around  the  speci- 
mens, leaving  a  margin  of  about  an  eighth  of  an  inch.  Trim  the 
top  surfaces  of  the  collodion  parallel  with  the  bottom  surfaces,  then 
dip  the  trimmed  surface  into  a  little  absolute  alcohol  contained  in 
a  watch-glass,  in  order  to  dehydrate  it.  This  will  take  about  two 
minutes.  Label  glass  blocks  with  lead-pencil,  place  a  drop  of 
thick  collodion  on  the  writing,  and  transfer  the  embedded  specimens 
immediately  from  the  absolute  alcohol  to  the  drop  of  collodion, 
pressing  it  into  contact  with  the  glass.  When  a  good  pellicle  has 
formed  on  the  collodion  drop  the  whole  block  into  80  per  cent, 
alcohol.  If  the  block  of  hardened  collodion  containing  the  speci- 
men be  sufficiently  dehydrated  on  the  surfaces  coming  in  contact 
with  the  drop  of  collodion,  and  the  latter  have  not  time  for  the 
formation  of  a  pellicle  before  it  receives  the  block,  there  will  be  no 
difficulty  in  cementing  the  embedded  specimen  to  the  roughened 
surface  of  the  glass.  It  is  best  not  to  cut  sections  until  the  day 
after  the  specimen  has  been  affixed  to  the  glass  block.  These 
blocks,  with  attached  specimens,  may  be  preserved  indefinitely  in 
80  per  cent,  alcohol. 

The  thin  coating  of  glycerin  on  the  inside  of  the  embedding-dish 
serves  the  purpose  of  preventing  the  collodion  from  sticking  to  the 
o'lass. 

2.  Embedding  in  Paraffin. — The  specimen  should  first  be  trimmed 
so  as  to  have  one  surface  parallel  to  the  plane  of  the  future  sections. 
If  it  is  surrounded  by  too  much  paraffin  to  permit  of  ready  inspec- 
tion, it  may  be  placed  on  a  piece  of  filter-paper  and  warmed  until 
the  superfluous  paraffin  is  absorbed  by  the  paper.  The  trimmed 
surface  is  then  laid  upon  a  small  glass  plate  that  has  been  smeared 


414  HISTOLOGICAL  TECHNIQUE. 

with  a  mere  trace  of  glycerin,  and  metallic  right-angles,  similarly 
smeared  on  the  inside,  are  placed  around  the  specimen  in  such  a  way 
as  to  form  a  box  with  a  clear  space  at  least  an  eighth  of  an  inch  broad 
between  its  sides  and  the  specimen.  Melted  paraffin,  at  a  temperature 
only  slightly  exceeding  that  necessary  to  keep  it  fluid,  is  then  poured 
into  the  box,  filling  it.  The  paraffin  should  now  be  made  to  cool 
as  rapidly  as  possible,  in  order  to  prevent  its  becoming  crystalline. 
For  this  reason  it  is  well  to  prepare  the  box  formed  by  the  plate  of 
glass  and  the  metallic  right-angles  in  the  bottom  of  a  deep  soup- 
plate  or  some  similar  vessel.  After  the  box  has  been  filled  with 
melted  paraffin  cold  water  may  be  poured  into  the  plate  until  its 
surface  is  nearly  on  a  level  with  the  top  of  the  box,  and  when  the 
top  of  the  paraffin  has  congealed  the  plate  may  be  filled  with  cold 
water.  After  a  few  minutes  the  box  may  be  taken  apart  and  the 
block  of  paraffin  left  in  the  water  to  become  cold. 

These  paraffin-blocks  may  be  labelled  with  a  needle  and  kept 
indefinitely  in  the  dry  condition,  at  a  temperature  below  that  at 
which  the  paraffin  softens.  When  they  are  to  be  used  the  bottom 
of  the  block  should  be  trimmed  parallel  with  the  top,  sufficient 
paraffin  being  removed  to  obliterate  the  hollow  which  formed  when 
the  paraffin  solidified.  This  trimmed  surface  is  then  made  to  ad- 
here to  the  paraffin-support  of  the  microtome,  or  a  block  of  hard 
wood,  by  means  of  a  heated  scalpel. 

It  often  happens  that  little  air-bubbles  are  present  in  the  paraffin 
close  to  the  specimen,  or  that  cracks  exist  between  the  specimen 
and  the  surrounding  paraffin,  owing  to  the  retention  of  a  little  air 
at  the  time  of  embedding.  These  defects  can  be  remedied  by  melt- 
ing the  paraffin  with  a  heated  needle.  It  is  important  that  the 
paraffin  should  everywhere  be  in  perfect  contact  with  the  specimen. 
When  this  repairing,  if  necessary,  has  been  done  and  the  paraffin 
has  become  cold  again,  the  block  should  be  trimmed  so  that  the 
specimen,  or  at  least  its  upper  part,  is  contained  in  a  little  cubical 
mass  resting  on  the  main  block,  with  a  margin  of  paraffin,  about 
1  mm.  thick  at  the  places  where  the  edges  of  the  cube  are  nearest 
to  the  specimen.  Those  edges  should  be  straight  and  at  right  angles 
to  each  other,  and  the  sides  of  the  trimmed  cube  should  be  vertical. 
In  trimming  the  block  only  thin  slices  should  be  removed  at  a  time, 
in  order  to  avoid  cracking  the  paraffin  forming  the  small  cubical 
mass  enclosing  the  specimen. 

These  manipulations  prepare  the  specimen  for  cutting. 


METHODS  OF  CUTTING.  415 

Methods  of  Cutting. 

It  is  possible  to  obtain  useful  sections  from  fresh  or  hardened 
tissues  by  free-hand  cutting  with  a  sharp  razor;  for  this  purpose  the 
razor  should  either  be  very  hollow  ground,  so  as  to  have  a  thin 
blade,  or  the  lower  surface  should  be  ground  flat.  In  stropping 
the  razor,  or  microtome-knife,  the  stroke  should  be  from  point  to 
heel  during  both  the  forward  and  return  motions.  In  cutting, 
the  edge  should  be  used  from  heel  to  point,  and  this  same  motion 
should  be  used  in  honing.  A  wire  arrangement  is  usually  furnished 
with  microtome-knives,  which  is  intended  for  use  while  honing  or 
stropping.  It  serves  to  raise  the  back  of  the  knife  when  the  flat 
side  is  sharpened,  and  should  always  be  employed.  Care  must  be 
taken  not  to  press  the  knife  against  the  strop,  as  this  is  liable  to 
turn  or  blunt  the  edge.  A  few  light  strokes  on  the  strop  immedi- 
ately after  each  day's  use  will  keep  the  knife  sharp  and  coat  it  with 
a  little  grease,  protecting  it  from  rust.  A  microtome-knife  should 
never  be  allowed  to  rest  with  its  edge  on  any  hard  surface  ;  the  mere 
weight  of  the  knife  is  sufficient  to  spoil  its  edge. 

In  cutting  free-hand  sections  of  fresh  tissues  the  upper  surface 
of  the  razor  should  be  kept  flooded  with  normal  (0.75  per  cent.) 
salt  solution.  The  sections  float  in  this  fluid  and  are  kept  from 
tearing.  Each  section  should  be  removed  by  a  single  stroke  of  the 
razor.  When  hardened  specimens  are  cut,  80  per  cent,  alcohol 
should  be  used  instead  of  salt  solution. 

Free-hand  sections  cannot  be  made  either  so  thin  or  uniform  as 
sections  prepared  with  a  microtome,  and  these  instruments  are  now 
so  cheap  that  they  are  universally  used.  There  are  three  principal 
forms:  1,  freezing-microtomes ;  2,  paraffin-microtomes;  3,  micro- 
tomes for  cutting  sections  of  tissues  embedded  in  collodion.  The 
last  are  often  fitted  with  attachments  intended  for  use  in  cutting 
frozen  sections,  and  can  also  be  used  for  paraffin.  But  the  best 
results  are  obtained  by  using  instruments  especially  designed  for 
each  purpose. 

1.  Frozen  Sections. — Freezing  is  usually  employed  when  sections  of 
fresh  tissues  are  to  be  made,  but  hardened  tissues  may  be  cut  with 
a  freezing-microtome  if  the  alcohol  be  first  removed  by  soaking  for 
a  considerable  time  in  water.  The  tissue  may  be  placed  upon  the 
plate  of  the  microtome  in  a  little  water  or  neutral  salt  solution  ;  but 
a  better  method  is  first  to  soak  the  tissue  in  a  syrupy  solution  of 


416  H1STOLOGICAL  TECHNIQUE. 

gum-arabic,  and  to  moisten  the  plate  with  the  same  before  freezing. 
This  solution  freezes  in  less  coarsely  crystalline  form  than  water  or 
salt  solution. 

When  the  tissues  are  frozen,  thin  sections  are  removed  with  a 
quick  forward  and  slightly  oblique  stroke  of  the  knife.  The  motion 
is  intermediate  between  that  of  a  plane  and  a  single  stroke  of  a  saw. 
The  sections  are  floated  from  the  knife  in  a  dish  of  water  or  normal 
salt  solution ;  or  they  may  be  fixed  in  a  4  per  cent,  solution  of  for- 
maldehyde. The  frozen  tissue  must  not  be  too  hard.  Should  that 
be  the  case,  the  upper  surface  may  be  moistened  by  means  of  a 
camePs-hair  brush,  dipped  in  water  or  salt  solution,  or  warmed 
with  the  breath. 

2.  Collodion-sections. — The  block  upon  which  the  embedded  speci- 
men is  fastened  is  secured  in  the  clamp  of  the  microtome  in  such 
a  position   that   the   sections  will  be  made   in   the  desired   plane. 
The  knife  is  then  adjusted  on  its  carrier  in  an  oblique  position,  so 
that  the  greatest  possible  length  of  its  edge  will  be  utilized  in  cut- 
ting.    The  upper  surface  of  the  knife  is  flooded  with  80  per  cent, 
alcohol,  and  slices  are  removed  with  the  knife  until  the  desired 
level  of  the  specimen  has  been  reached.     Sections  are  then  made 
as  thin  as  is  compatible  with  obtaining  complete  sections  from  the 
whole  surface.     The  sections  float  in  the  80  per  cent,  alcohol,  with 
which  the  knife  should  be  kept  flooded,  and  may  be  removed  with 
a  camel's-hair  brush.     At  no  time  should  either  the  knife  or  the 
specimen  be  allowed  to  dry.     The  sections  may  be  kept  indefinitely 
in  80  per  cent,  alcohol,  or  they  may  be  dropped  into  water  if  they 
are  to  be  used  within  a  short  time. 

After  use,  the  knife  should  be  carefully  wiped,  stropped,  and  placed 
in  its  case.  The  microtome  should  be  dried  and  the  tracks  moistened 
with  a  little  oil  of  sweet  almonds  or  paraffin  oil,  to  prevent  rusting. 

3.  Paraffin-sections. — The  knife  should  be  fixed  perpendicular  to 
the  direction  of  cutting,  its  edge  acting  like  that  of  a  plane.     Its 
surfaces  must  be  clean  and  dry ;  adherent  paraffin  can  be  removed 
with  a  cloth  moistened  with  xylol. 

The  paraffin-block  containing  the  specimen  to  be  cut  is  firmly 
clamped  with  one  of  its  narrow  edges  parallel  to  the  edge  of  the 
knife.  The  block  is  now  raised  and  moderately  thick  slices  re- 
moved until  the  desired  level  is  reached,  when  the  thin  sections 
desired  may  be  cut.  It  not  infrequently  happens  that  the  sections 
roll  before  the  edge  of  the  knife.  This  is  probably  due  to  the 


METHODS  OF  CUTTING.  417 

paraffin  being  too  hard.  In  that  case  the  cutting  should  be  done  in 
a  warmer  room.  This  rolling  will,  however,  cause  little  trouble  in 
the  use  of  the  sections  unless  it  be  desired  to  have  them  adhere  to 
each  other  at  the  edges  to  form  ribbons,  in  which  the  succession  of 
the  sections  is  preserved. 

Before  paraffin-sections  can  be  stained  it  is  necessary  to  remove 
the  paraffin.  If  the  tissues  are  sufficiently  coherent,  this  can  be 
done  by  dropping  the  sections  into  xylol  or  chloroform  ;  but  if  this 
would  cause  a  disintegration  of  the  sections,  they  must  be  affixed  to 
slides  or  cover-glasses  by  means  of  a  cement  which  shall  hold  the  dif- 
ferent parts  of  the  tissues  in  their  proper  relative  positions  after  the 
paraffin  has  been  removed.  The  simplest  cement  for  this  purpose 
is  Mayer's  albumin  mixture,  prepared  as  follows  :  beat  up  the  white 
of  an  egg  and  allow  the  froth  to  liquefy.  Then  add  an  equal  bulk 
of  glycerin  and  a  few  pieces  of  camphor  (for  the  preservation  of 
the  mixture).  This  cement  is  applied  to  the  clean  surface  of  a 
slide,  or,  better,  a  cover-glass,  in  a  very  thin  layer  with  the  side  of 
a  camePs-hair  brush,  care  being  taken  to  leave  no  air-bubbles. 
The  paraffin-sections  are  removed  from  the  knife  with  a  fine 
camePs-hair  brush  or  a  small,  but  rather  stiff,  feather  inserted  into 
a  handle,  and  placed  upon  the  coating  of  cement.  They  are  then  flat- 
tened out  with  the  brush  or  feather  and  pressed  against  the  glass  to 
remove  superfluous  cement.  If  the  sections  have  rolled,  unrolling  will 
be  facilitated  by  warming  the  sections  with  the  breath.  The  cover- 
glasses  are  set  aside  to  dry  a  little,  and  are  then  heated  to  render 
the  albumin  insoluble.  This  requires  some  practice.  The  manipu- 
lation is  intended  to  accomplish  the  following  results  :  the  paraffin 
melts  at  a  lower  temperature  than  that  at  wrhich  the  albumin  is 
coagulated,  and  this  fact  is  utilized  to  remove  all  excess  of  the 
cement,  which  is  washed  away  from  the  tissues  by  the  flow  of  melted 
paraffin.  The  residual  albumin  is  sufficient  to  make  the  section 
adhere  to  the  glass  when  subjected  to  a  high  enough  temperature  to 
cause  its  coagulation.  The  albumin  should  be  dried  to  a  consider- 
able extent  before  it  is  converted  by  the  heat  into  its  insoluble  form, 
otherwise  it  will  coagulate  in  opaque  masses.  To  bring  about  the 
desired  results  the  cover-glass,  held  in  a  pair  of  forceps,  is  waved 
over  a  flame  until  the  paraffin  is  seen  to  melt.  That  tempera- 
ture is  maintained  for  a  few  moments,  and  then  the  cover-glass 
is  heated  until  vapors  are  distinctly  seen  to  rise  from  its  surface. 
Great  care  must  be  taken  not  to  scorch  the  sections.  When  the 

27 


418  HISTOLOGICAL   TECHNIQUE. 

sections  have  been  cemented  to  them  the  cover-glasses  are  placed  in 
absolute  alcohol  to  dehydrate  them,  and  are  then  treated  with  xylol, 
chloroform,  or  some  other  solvent  of  paraffin.  The  solvent  is  then 
removed  by  another  bath  of  absolute  alcohol,  and  the  alcohol 
removed  by  water,  when  the  sections  are  ready  for  staining. 

When  the  sections  do  not  require  affixing  to  cover-glasses  they 
may  be  dropped  into  the  solvent  for  the  paraffin,  and  the  latter 
removed  with  absolute  alcohol,  for  which  water  is  then  substituted, 
preparing  the  sections  for  staining.  It  sometimes  happens  that 
when  sections  are  transferred  from  absolute  alcohol  to  water  the 
diffusion-currents  are  so  strong  that  the  sections  are  destroyed. 
When  this  is  the  case  the  transition  must  be  made  more  gradually, 
baths  of  80  per  cent.,  50  per  cent.,  and  30  per  cent,  alcohol  being 
interposed  between  the  absolute  alcohol  and  the  water. 

Methods  of  Staining. 

A  large  number  of  methods  have  been  devised  for  bringing  out 
the  structure  of  tissues.  Many  of  the  methods  are  of  almost  uni- 
versal application,  while  others  require  special  methods  of  fixa- 
tion or  other  preliminary  treatment  of  the  tissues.  Some  are  calcu- 
lated to  render  the  general  features  of  structure  more  evident  than 
they  would  be  if  the  tissues  were  not  stained ;  others  stain  certain 
elements  some  characteristic  color,  and,  to  that  extent,  serve  the 
purpose  of  microchemical  reagents.  Only  a  few  of  the  more  useful 
methods  can  be  described  here ;  for  others  the  reader  is  referred  to 
the  larger  text-books  and  the  technical  journals. 

1.  Hsematoxylin  and  Eosin. — Hsematoxylin,  the  coloring-principle 
of  logwood,  has  proved  a  very  useful  stain  for  the  nuclei  of  cells.  It 
is  not  a  pure  nuclear  stain,  but  also  tints  the  cytoplasm  of  cells  and 
the  intercellular  substances.  It  is  most  commonly  employed  in 
combination  with  alum.  Such  combinations  of  coloring-matter 
with  a  base  are  called  "  lakes." 

A  hsematoxylin-lake  may  be  used  alone,  or  its  use  may  be  preceded 
or  followed  by  the  employment  of  a  counterstain  with  some  diffuse 
color  not  affecting  the  nuclei.  For  counterstaining,  eosin  or  neutral 
carmine  is  usually  employed.  Both  stain  the  tissues  a  diffuse  red, 
varying  in  depth  according  to  the  nature  of  the  tissue-elements  in 
the  section. 

There  are   several  formulae  for  the  preparation  of  alum-hsema- 


METHODS  OF  STAINING.  419 

toxylin,  but  that  devised  by  Bohmer  will  answer  all  purposes,  and 
is  very  simple  : 

1.  Hsematoxylin  crystals,  1  gram. 
Absolute  alcohol,                               10  cc. 

2.  Alum,  20  grams. 
Distilled  water,                                 200  cc. 

Cover  the  solutions  and  allow  them  to  stand  over  night.  The 
next  day  mix  them  and  allow  the  mixture  to  stand  for  one  week 
in  a  wide-mouthed  bottle  lightly  plugged  with  cotton.  Then  filter 
into  a  bottle  provided  with  a  good  cork.  The  solution  is  then 
ready  for  use.  Nearly  all  solutions  of  alum-hsematoxylin  require 
an  interval  of  time  for  "  ripening,"  and  their  staining-powers 
improve  with  age. 

Alum-hsematoxylin  is  intended  for  staining  sections  from  tissues 
that  have  been  fixed  and  hardened.  It  is  especially  useful  when 
the  fixing-solution  employed  contained  chromates,  but  may  be  used 
after  almost  any  method  of  fixation,  if  the  time  of  staining  is  of 
the  right  length  and  the  sections  are  previously  freed  from  acidity 
by  thorough  washing. 

If  the  following  directions  are  closely  adhered  to,  the  student 
can  hardly  fail  to  obtain  good  results  in  the  use  of  Bohmer's 
hsematoxylin  : 

Transfer  the  sections  from  the  80  per  cent,  alcohol  in  which  they 
have  been  kept  to  a  dish  of  distilled  water.  At  first  they  will  float 
on  the  surface  of  the  water  ;  this  is  a  favorable  moment  for  removing 
all  folds  and  wrinkles.  The  sections  should  be  manipulated  with 
platinum  needles,  prepared  by  fusing  a  bit  of  platinum  wire  into 
the  end  of  a  glass  rod.  Such  needles  can  be  cleaned  by  heating 
the  wire  red  in  a  flame. 

When  the  sections  sink  to  the  bottom  of  the  dish  of  water,  and 
remain  there,  it  may  be  assumed  that  they  are  free  from  alcohol. 

Filter  about  5  cc.  of  the  hsematoxylin  into  a  watch-glass  or  butter- 
dish and  transfer  the  sections  from  the  water  to  the  dye. 

Let  the  sections  stain  for  three  minutes  by  the  watch,  and  then 
transfer  them  to  a  dish  of  distilled  water.  At  first  the  sections  will 
have  a  reddish  tint,  but  as  the  washing  proceeds  the  color  will  turn 
to  a  pure  blue.  During  the  washing  the  water  should  be  renewed, 
until  finally  it  acquires  no  color  from  the  sections  and  the  latter 


420  HISTOLOGICAL   TECHNIQUE. 

have  lost  all  traces  of  a  red  tint.  This  washing  may  take  several 
minutes,  or  even  a  few  hours ;  but  if  good,  permanent  stains  are 
desired,  it  is  of  great  importance  that  it  be  thorough.  This  wash- 
ing completes  the  actual  staining  with  hsematoxylin,  and  the  sections 
are  then  ready  for  counterstaining  with  eosin  or  for  dehydration. 

The  eosin  solution  used  for  diffuse  staining  is  prepared  by  dis- 
solving 1  gram  of  eosin  in  60  cc.  of  50  per  cent,  alcohol.  Of  this 
solution,  about  ten  drops  are  added  to  5  cc.  of  distilled  water  in  a 
small  dish ;  the  sections  are  stained  for  about  five  minutes  and  then 
washed  in  distilled  water.  They  are  then  ready  for  dehydration 
and  mounting.  The  diluted  eosin  should  be  thrown  away  after  use, 
but  the  hsematoxylin  can  be  filtered  back  into  the  stock-bottle. 

Since  the  hsematoxylin  solution  improves  with  age,  no  exact 
directions  can  be  given  as  to  the  length  of  time  sections  should 
remain  in  a  particular  solution.  Three  minutes  will  usually  yield 
good  results ;  but  if  it  is  found  that  the  color  is  too  dark,  a  shorter 
time  should  be  employed,  and  vice  versd.  One  soon  becomes  famil- 
iar with  the  staining-powers  of  the  particular  solution  used.  The 
dishes  that  have  contained  ha?matoxylin  should  be  washed  soon 
after  use,  or  may  be  subsequently  cleaned  with  a  little  hydrochloric 
acid,  all  traces  of  which  should  then  be  removed  by  thorough  wash- 
ing in  water. 

The  above  method  for  staining  with  hsematoxylin  and  eosin  is 
highly  recommended  for  general  routine  work. 

2.  Neutral  Carmine. — 

Carmine,  "No.  40,"  1  gram. 

Distilled  water,  50  cc. 

Ammonia,  5   " 

The  solution  is  allowed  to  remain  exposed  to  the  air  until  the 
odor  of  ammonia  is  no  longer  perceptible.  It  is  then  filtered  into 
a  bottle,  where  it  is  kept  till  needed. 

Neutral  carmine  gives  a  diffuse  stain,  resembling  that  of  eosin, 
but  rather  clearer  in  character.  It  is  employed  in  a  greatly  diluted 
form,  according  to  the  following  directions : 

One  drop  of  the  neutral  carmine  is  mixed  with  about  20  cc.  of 
distilled  water.  A  trace  of  acetic  acid  is  then  added  by  dipping  a 
platinum  needle  into  the  acid  and  stirring  the  diluted  dye  with  the 
acidulated  needle.  A  piece  of  filter-paper  is  then  placed  upon  the 


METHODS  OF  STAINING.  421 

bottom  of  the  dish,  and  the  sections  to  be  stained  are  transferred 
from  distilled  water  to  the  dye  and  distributed  upon  the  paper  in 
such  a  way  that  they  do  not  lie  over  each  other.  The  dye  acts 
very  slowly,  twenty-four  hours  being  none  too  long  for  good  results. 
If  the  staining  be  hastened  by  using  a  stronger  solution,  it  suffers 
in  sharpness.  After  staining,  the  sections  are  thoroughly  washed 
in  distilled  water,  and  may  then  be  subjected  to  a  nuclear  dye,  such 
as  hsematoxylin.  The  proper  acidulation  of  the  diluted  dye  is  of 
importance  for  the  success  of  this  method.  If  the  solution  is  not 
sufficiently  neutralized,  the  sections  will  not  be  stained ;  if  it  is  too 
acid,  precipitation  of  the  carmine  will  take  place. 

3.  Alum-carmine. — 

Alum,  5  grams. 

Distilled  water,  100  cc. 

Carmine,  "  No.  40,"  2  grams. 

The  alum  is  dissolved  in  the  water  with  the  aid  of  heat,  the 
carmine  then  added,  and  the  mixture  kept  at  the  boiling-point  for 
about  half  an  hour.  It  is  then  allowed  to  cool  and  filtered  into  the 
stock-bottle.  Two  or  three  drops  of  deliquesced  carbolic  acid  may 
be  added  to  prevent  the  development  of  fungi. 

Sections  are  stained  in  the  undiluted,  but  filtered,  dye  for  at  least 
five  minutes.  There  is  no  danger  of  over-staining.  It  is  a  pure 
nuclear  stain,  coloring  the  chromatin  red.  After  staining,  the  sec- 
tions are  either  washed,  and  are  then  ready  for  dehydration,  or 
they  may  receive  a  counterstain  with  picric  acid,  coloring  the  tissues 
a  diffuse  yellow.  This  may  be  most  readily  accomplished  by  adding 
a  few  small  crystals  of  picric  acid  to  the  first  dish  of  dehydrating 
alcohol  (see  p.  428). 

4.  Borax-carmine. — 

Borax,  4  grams. 

Distilled  water,  100  cc. 

Carmine,  "  No.  40,"  3  grams. 

Alcohol,  70  per  cent.,  100  cc. 

The  borax  is  dissolved  in  the  water  by  warming,  and  the  solution 
allowed  to  cool ;  the  carmine  is  then  stirred  in  and  the  alcohol  added. 
After  standing  twenty-four  hours  the  solution  is  filtered  into  the 
stock-bottle,  a  process  that  is  exceedingly  slow. 


422  HISTOLOGICAL  TECHNIQUE. 

Borax-carmine  is  used  for  the  staining  of  little  masses  of  tissue 
before  they  are  embedded.  It  is  a  nuclear  dye,  giving  the  chromatin 
a  red  color.  It  is  useful  when  paraffin-embedding  is  to  be  employed 
and  it  is  desirable  to  restrict  the  manipulation  of  the  sections  to  a 
minimum. 

Small  pieces  of  hardened  tissues,  not  over  5  mm.  thick,  are  trans- 
ferred from  distilled  water  to  the  undiluted  dye  and  allowed  to  stain 
for  twenty-four  hours,  or  longer.  After  staining  they  are  immedi- 
ately placed  in  an  acid  alcohol,  prepared  by  adding  5  drops  of  con- 
centrated hydrochloric  acid  to  100  cc.  of  70  per  cent,  alcohol.  The 
tissue  should  not  rest  on  the  bottom  of  the  vessel  containing  the 
alcohol,  but  upon  crumpled  filter-paper,  so  that  the  extracted  excess 
of  coloring-matter  may  sink  to  the  bottom.  If  the  acid  alcohol 
around  the  specimen  becomes  colored,  fresh  portions  of  alcohol 
should  be  used.  The  treatment  with  acid  alcohol  is  continued  until 
no  more  color  is  given  off  from  the  specimen.  It  is  then  transferred 
to  90  per  cent,  alcohol,  in  which  it  should  remain  for  twenty- 
four  hours,  after  which  it  can  be  subjected  to  the  dehydration  neces- 
sary for  embedding. 

5.  Orth's  Lithio-carmine. — 

Carmine,  "  No.  40,"  3  grams. 

Lithium  carbonate,  saturated  aqueous  solution,  100  cc. 

The  solution  of  lithium  carbonate  is  prepared  by  occasionally 
shaking  a  mixture  of  distilled  water  and  an  excess  of  lithium  car- 
bonate. Twenty-four  hours  will  suffice  for  the  production  of  a 
strong  enough  solution.  The  supernatant  liquid  is  then  filtered. 
Carmine  readily  dissolves  in  this  solution.  For  preservation  a 
crystal  of  thymol  may  be  added. 

Lithio-carmine  stains  sections  in  about  five  minutes,  and  there  is 
no  danger  of  overstaining.  Like  borax-carmine,  it  requires  after- 
treatment  with  acid  alcohol.  The  sections  should  be  transferred, 
without  intermediate  washing,  to  70  per  cent,  alcohol  containing  1 
per  cent,  of  concentrated  hydrochloric  acid ;  they  may  then  be  de- 
hydrated, and,  if  desired,  counterstained  with  picric  acid  during  the 
dehydration. 

6.  Unna's  Methylene-blue. — 

Methylene-blue,  1  gram. 

Potassium  carbonate,  1      " 

Distilled  water,  100  cc. 


METHODS  OF  STAINING.  423 

When  required  for  use,  this  solution  should  be  diluted  with  dis- 
tilled water  to  about  one-tenth  of  its  strength.  It  is  a  good  stain  for 
bacteria,  and  may  also  be  used  for  staining  the  nuclei  of  tissues 
either  by  itself,  or  after  using  eosin  as  a  diffuse  stain.  An  aqueous 
solution  of  eosin,  5  per  cent.,  is  used  for  this  purpose,  the  sections 
being  stained  for  about  five  minutes.  They  are  then  washed  to 
remove  the  excess  of  eosin,  and  stained  in  the  diluted  methylene- 
blue  for  about  an  hour.  After  this  they  are  again  washed  and 
treated  with  absolute  alcohol,  which  discharges  the  excess  of  blue. 
They  are  then  cleared  with  xylol  and  mounted  in  dammar  or 
Canada  balsam,  dissolved  in  xylol.  The  preliminary  staining  with 
eosin  may  be  omitted,  when  a  contrast-  or  counters.tain  is  not 
required. 

7.  Aqueous  Methylene-blue. — This  is  usually  prepared  at  the  time 
when  needed  by  mixing  one  part  of  a  saturated  solution  of  the  ani- 
1  in-color  in  95  per  cent,  alcohol  with  nine  parts  of  distilled  water. 
It  is  frequently  employed  as  a  general  stain  for  bacteria. 

Other  anilin-colors,  such  as  fuchsin,  gentian-violet,  methyl-violet, 
and  Bismarck-brown,  may  be  kept  in  concentrated  alcoholic  solu- 
tion, to  be  diluted  in  a  similar  manner  just  before  use.  When  these 
solutions  are  used  for  staining  sections  or  cover-glass  preparations 
the  adherent  dye  is  washed  off  with  water,  after  which  the  intensity 
of  the  stain  is  reduced  by  the  use  of  alcohol,  95  per  cent,  or  abso- 
lute, which  bleaches  the  portions  of  the  specimen  which  retain  the 
color  with  the  least  tenacity.  If  the  action  of  the  alcohol  be  main- 
tained for  too  long  a  time,  the  color  may  be  discharged  from  all 
parts  of  the  specimen.  The  method  of  overstating  a  specimen, 
and  then  discharging  the  color  from  those  parts  where  it  is  not  de- 
sired, is  a  common  one.  The  process  of  discharging  the  color  is 
called  the  "  differentiation  "  of  the  stain,  because  it  serves  to  dis- 
tinguish those  elements  which  hold  the  color  strongly  from  those 
which  part  with  it  easily. 

8.  Carbol-fuchsin. — 

Saturated  alcoholic  solution  of  fuchsin,  10  cc. 

Aqueous  solution  of  carbolic  acid  crystals,  5  per  cent.,     90  cc. 

This  solution  should  always  be  carefully  filtered  before  use. 

9.  Anilin-gentian-violet. — A.  Ehrlich's  formula  : 

Saturated  alcoholic  solution  of  gentian- violet,  1.5  cc. 

Freshly  prepared  anilin-water,  8.5  cc. 


424  HISTOLOGICAL   TECHNIQUE. 

The  anilin-water  is  prepared  by  shaking  a  few  drops  of  anilin 
with  distilled  water,  allowing  the  mixture  to  stand  for  about  ten 
minutes,  and  then  filtering  through  well-moistened  filter-paper. 
The  filtrate  should  contain  no  globules  of  the  anilin.  In  order  to 
avoid  this  the  filtration  should  be  stopped  before  all  the  watery 
part  of  the  mixture  has  run  through  the  paper,  otherwise  oily  drops 
of  anilin  will  follow. 

Precipitates  are  likely  to  occur  in  this  gentian-violet  solution 
when  it  is  first  prepared.  After  twenty-four  hours  these  are  less 
abundant.  The  solution  deteriorates  soon  after  that  time,  and 
should  not  be  used  more  than  a  week  after  its  preparation. 

B.  Stirling's  formula : 

Gentian-violet,  5  grams. 

Alcohol,  10  cc. 
Anilin,  2  cc. 

Distilled  water,  88  cc. 

This  solution  keeps  better  than  the  preceding.  Both  must  be 
filtered  carefully  through  moistened  filter-paper  immediately  before 
being  used. 

10.  Gram's  Solution. — This  is  a  differentiating  agent  used  in  con- 
nection with  anilin-gentian-violet : 

Iodine,  1  gram. 

Potassium  iodide,  2  grams. 

Distilled  water,  300  cc. 

The  specimens  are  first  overstained  with  the  gentian- violet  solu- 
tion. They  are  then  washed  in  water  and  placed  in  Gram's  solution 
for  from  three  to  five  minutes.  While  in  this  solution  they  turn  a 
brown  color,  and  the  combination  between  the  coloring-matter  and 
some  of  the  elements  of  the  specimen  is  loosened.  The  specimen 
is  then  transferred  to  95  per  cent,  alcohol,  in  which  it  remains  until 
no  more  color  is  given  off.  If  sufficient  color  has  not  been  removed, 
the  treatment  with  Gram's  solution  and  alcohol  may  be  repeated. 
After  this  differentiation  the  specimen  may  be  dehydrated,  cleared, 
and  mounted ;  or  a  contrast-stain  may  be  used  before  those  manipu- 
lations. This  is  a  useful  method  for  staining  bacteria  in  sections 
of  tissue  when  the  species  of  bacteria  are  such  as  resist  the  decolor- 
izing action  of  the  iodine.  In  this  respect  different  species  of  bac- 


METHODS  OF  STAINING.  425 

teria  differ  greatly,  and  the  method  is  commonly  employed  in  bac- 
teriological work  to  distinguish  those  species  which  retain  the  stain, 
or  are  "  positive  to  Gram,"  from  those  which  are  decolorized  or 
"  negative  to  Gram." 

11.  Van  Giesson's  Picric  Acid  and  Acid  Fuchsin  Stain. — 

Aqueous  solution  of  acid  fuchsin,  1  per  cent.,  5  cc. 

Saturated  aqueous  solution  of  picric  acid,  100    " 

This  solution  serves  to  stain  fibrous  intercellular  substances.  It 
is  used  in  the  following  manner : 

1.  Slightly  overstain  with  alum   hsematoxylin;  e.  g.,  Bohmer's 
hsematoxylin. 

2.  Wash  thoroughly  in  distilled  water. 

3.  Stain  in  Van  Giesson's  dye  for  five  minutes. 

4.  Wash  in  water. 

5.  Dehydrate  in  95  per  cent,  alcohol. 

6.  Clear  in  oil  of  origanum. 

7.  Mount  in  xylol-balsam  or  xylol-dammar. 

The  tissues  should  have  been  fixed  in  a  corrosive-sublimate  solu- 
tion or  one  containing  chromates ;  e.  g.,  Muller's  fluid,  Zenker's 
fluid,  or  sublimate  solution.  The  connective-tissue  fibres  are  stained 
red  by  the  acid  fuchsin.  The  reason  for  overstating  with  hsema- 
toxylin is  that  subsequent  treatment  with  picric  acid  discharges 
some  of  that  color. 

12.  Benda's   Iron-hsematoxylin   Stain. — This  is  a  powerful  stain 
well  adapted  to  the  staining  of  paraffin-sections  that   have   been 
affixed  to  cover-glasses.      It  stains  nuclei  and   intercellular   sub- 
stances, as  well  as  the  protoplasm  of  cells,  various  shades  of  gray, 
and  the  color  is  very  permanent.     The  outline  of  the  method  is  as 
follows : 

1.  Mordant  the  sections  (after  affixing  to  cover-glasses,  if  that 
method  is  used)  in  a  mixture  of  equal  parts  of  liquor  ferri  sul- 
furici  oxydati  of  the  German  Pharmacopoeia  and  distilled  water  for 
twenty-four  hours. 

2.  Rinse  in  distilled  water,  and  then  wash  in  three  changes  of 
tap-water. 

3.  Stain  in  aqueous  solution  of  haematoxylin,  prepared  by  mix- 
ing 10  drops  of  a  concentrated  alcoholic  solution  of  the  crystals 
with  10  cc.  of  distilled  water.     Stain  for  from  one-half  to  twenty- 
four  hours. 


426  HISTOLOGICAL  TECHNIQUE. 

4.  Rinse  in  distilled  water. 

5.  Differentiate  in  equal  parts  of  glacial  acetic  acid  and  distilled 
water. 

6.  Wash  thoroughly  in  distilled  water. 

7.  Dehydrate  in  absolute  alcohol. 

8.  Clear  in  xylol,  carbol-xylol,  or  some  essential  oil. 

9.  Mount  in  balsam. 

13.  Pal's  Modification  of  Weigert's  Stain  for  the  Medullary  Sheath 
of  Nerves. — This  method  is  useful  for  the  study  of  the  central  ner- 
vous system,  and  may,  with  advantage,  be  preceded  by  staining 
with  neutral  carmine.  The  tissues  should  have  been  fixed  in  a 
chromate  solution ;  e.  g.,  Miiller's  fluid. 

1.  Soak  sections  several  hours  in  1  per  cent,  chromic  acid  solu- 
tion in  water. 

2.  Stain  twenty- four  to  forty-eight  hours  in  : 

Hematoxylin  crystals,  1  gram, 

Absolute  alcohol,  10  cc. 

Lithium  carbonate  (saturated  aqueous  solution),  7    " 
Distilled  water,  90   " 

The  hymatoxylin  crystals  may  be  dissolved  in  the  alcohol  and 
the  solution  kept  in  stock,  the  proper  proportions  of  lithium  carbon- 
ate solution  and  water  being  added  at  the  time  of  use. 

3.  Wash  in  water  to  which  a  little  lithium  carbonate  solution  has 
been  added  (about  2  cc.  to  each  100  cc.  of  water).     The  sections 
should  acquire  a  deep-blue  color. 

4.  Diiferentiate  in  0.25  per  cent,  solution  of  potassium  perman- 
ganate in  distilled  water,  till  the  gray  matter — e.  </.,  of  the  spinal 
cord — becomes  brownish-yellow  (one-half  to  five  minutes). 

5.  Decolorize  the  gray  matter  in  the  following  solution  : 

Oxalic  acid,  1  gram, 

Potassium  sulphite,  1      " 

Distilled  water,  200  cc. 

6.  Wash  thoroughly  in  distilled  water. 

7.  Dehydrate  in  95  per  cent,  alcohol. 

8.  Clear  in  carbol-xylol,  oil  of  bergamot,  or  oil  of  origanum. 

9.  Mount  in  xylol-balsam  or  xylol-dammar. 

This  method  stains  the  myelin-sheaths  of  the  medullated  nerve- 


METHODS  OF  STAINING.  427 

fibres  a  dark  blue,  nearly  black,  color.  If  it  has  been  preceded  by 
a  stain  with  neutral  carmine,  the  axis-cylinders  of  the  nerve-fibres 
will  be  stained  red,  and  the  nuclei  of  the  nerve-cells  will  also 
appear  red. 

14.  Golgi's  Methods. — These  methods  have  yielded  most  excel- 
lent results  in  the  study  of  the  central  nervous  system,  the  dis- 
tribution of  the  peripheral  nerves,  and  the  delicate  terminations 
of  the  ducts  of  glands ;  e.  g.,  the  bile-capillaries.  The  methods 
must  be  regarded  as  special  procedures  in  such  studies,  and  can 
but  be  referred  to  here.  They  all  depend  upon  hardening  in  some 
chromium  salt,  with  or  without  the  addition  of  osmic  acid,  and  the 
subsequent  impregnation  with  silver  nitrate.  A  precipitate  is  thus 
produced  on  or  within  certain  of  the  elements  in  the  specimen,  giving 
them  a  dark-brown  or  black  color.  The  methods  are  capricious, 
and  not  all  of  the  tissue-elements  of  like  character  in  the  specimen 
are  rendered  prominent.  This  is  an  advantage,  but  necessitates 
a  degree  of  care  in  the  interpretation  of  the  results.  Furthermore, 
irrelevant  precipitates  may  form  in  the  tissues  which  have  no 
definite  relations  to  any  structure.  Considerable  practice  is,  there- 
fore, required  for  the  successful  employment  of  all  these  methods, 
not  only  for  a  satisfactory  execution  of  the  manipulations,  but  also 
in  the  study  of  the  results.  The  methods  have  no  value  for  the 
study  of  cell-structure,  since  the  whole  cell  is  either  covered  or 
filled  with  the  precipitates  formed  during  the  impregnation  with 
silver. 

Golgi  has  divided  his  methods  into  three  groups :  the  slow,  the 
rapid,  and  the  mixed.  For  the  details  of  these  methods  and  of 
the  various  modifications  introduced  by  different  investigators  the 
student  is  referred  to  the  journals  on  microscopy.  It  must  suffice 
to  state  here  that  the  slow  method  begins  with  a  hardening  of  the 
tissues  in  a  2  per  cent,  solution  of  potassium  bichromate,  which  is 
gradually  raised  to  5  per  cent.  This  hardening  takes  from  fifteen 
days  to  three  months.  In  the  rapid  method  the  tissues  are  first 
hardened  in  a  mixture  of  4  parts  of  a  2  per  cent,  solution  of  potas- 
sium bichromate  and  1  part  of  a  1  per  cent,  solution  of  osmic  acid. 
The  tissues  remain  in  this  mixture  for  from  two  to  six  days,  when 
they  are  ready  for  impregnation.  For  either  method  the  pieces 
of  tissue  should  not  be  thicker  than  1.5  cm. 


428  HISTOLOGICAL  TECHNIQUE. 

Methods  of  Dehydration. 

The  final  manipulation  in  nearly  all  the  methods  for  staining 
described  above  is  a  washing  of  the  sections  in  water.  This  water 
must  be  removed  before  permanent  mounts  can  be  made.  Dehy- 
dration is  accomplished  by  treating  the  sections  with  alcohol.  If 
they  are  impregnated,  or  have  been  embedded  in  collodion  or  eel- 
loidin,  they  must  not  be  dehydrated  in  absolute  alcohol,  as  that  dis- 
solves the  collodion.  In  such  cases  95  per  cent,  alcohol  is  employed, 
the  sections  being  treated  with  two  baths  of  alcohol.  When  sections 
have  been  stained  with  carmine  a  contrast-stain  may  be  obtained  by 
adding  a  few  small  crystals  of  picric  acid  to  the  first  dish  of  dehy- 
drating alcohol.  The  excess  of  picric  acid  is  then  removed  by  the 
alcohol  in  the  second  dish.  Absolute  alcohol  may  be  used  for  dehy- 
dration when  the  sections  have  not  been  embedded  in  collodion  or 
celloidin. 

When  anilin-dyes  have  been  used  to  stain  sections  it  must  be 
borne  in  mind  that  alcohol  not  merely  dehydrates,  but  also  differ- 
entiates the  stain.  If  the  sections  are  left  too  long  in  the  alcohol, 
they  may  lose  more  color  than  is  desired. 

Sections  that  are  to  be  mounted  in  glycerin  or  glycerin-jelly 
require  no  dehydration,  but  can  be  mounted  directly  from  water. 

Methods  of  Clearing. 

Clearing  is  necessary  when  specimens  are  to  be  permanently 
mounted  in  Canada  balsam  or  dammar.  Its  object  is  to  impreg- 
nate the  section  with  some  liquid  that  will  drive  out  alcohol  and 
also  be  miscible  with  the  resin  used  for  mounting.  Of  these  clear- 
ing-agents there  is  a  large  number,  from  which  a  choice  must  be 
made  according  to  the  method  of  embedding  that  has  been  employed 
and  the  nature  of  the  dye  with  which  the  tissues  have  been  stained. 
Clearing-agents  also  differ  in  their  miscibility  with  water,  some 
requiring  dehydration  with  absolute  alcohol,  others  clearing  well 
when  95  per  cent,  alcohol  has  been  used  for  dehydration. 

1.  Xylol. — This  is  an  excellent  clearing-agent  when  the  sections 
have  been  well  dehydrated  with  absolute  alcohol.  It  does  not 
injure  anilin-dyes.  It  is,  perhaps,  the  best  clearing-agent  for 
sections  of  tissue  stained  with  borax-carmine  before  cutting,  when 
no  counter-stain  is  employed.  Xylol  then  both  removes  the  paraffin 
in  the  section  and  clears  it. 


METHODS  OF  MOUNTING.  429 

2.  Carbol-xylol.— 

Carbolic  acid  crystals  (melted),  1  vol. 

Xylol,  3  vols. 

This  mixture  is  much  more  tolerant  of  water  than  pure  xylol. 
Sections  dehydrated  in  95  per  cent,  alcohol  may  be  cleared  with 
this  reagent,  which  does  not  dissolve  collodion.  The  carbolic  acid 
used  should  be  pure,  but  need  not  be  the  more  expensive  synthetic 
product. 

3.  Oil  of  Bergamot. — This  light-green  essential  oil  clears  well  and 
does  not  dissolve  collodion.      It  may  be  used  when  95  per  cent, 
alcohol  has  been  employed  for  dehydrating. 

4.  Oil  of  Origanum. — The  oleum  origani  cretici  should  be  used. 
It  is  of  light-brown  color  and  clears  sections  dehydrated  in  95  per 
•cent,  alcohol  or  stronger.     It  slowly  discharges  anilin-colors. 

5.  Oil  of   Cloves. — This   clearing-agent   dissolves   collodion  and 
discharges  anilin-colors.     It  may  be  used  when  it  is  desired  to  get 
rid  of  the  collodion  used  for  embedding  after  the  sections  have  been 
stained.     This  removal  is  favored  by  dehydration  in  absolute  alcohol 
before  clearing. 

6.  Oil  of  Cedar- wood. — This,  when  pure,  has  a  very  light-yellow 
color  and  smells  like  cedar-wood.     It  should  be  free  from  the  more 
pungent  odor  of  the  oil  derived  from  the  leaves.     This  essential 
oil  does  not  discharge  anilin-colors,  and  is,  therefore,  useful  when 
those  dyes  have  been  employed.     It  clears  slowly,  but  well,  and 
may  be  used  after  dehydration  with  95  per  cent,  alcohol. 

Methods  of  Mounting. 

Sections  that  have  been  treated  by  the  foregoing  methods  of 
preparation  are  fitted  for  mounting  in  a  solution  of  some  resin. 
The  most  commonly  employed  are  Canada  balsam  and  dammar. 
The  best  solvent  for  these  resins  is  xylol,  though  chloroform  and 
benzol  are  sometimes  used  for  this  purpose.  All  traces  of  turpen- 
tine should  be  removed  from  the  balsam  before  its  solution,  to  avoid 
the  discharge  of  stains  with  hsematoxylin  or  anilin-dyes  which  tur- 
pentine occasions. 

When  sections  are  transferred  from  alcohol  to  a  clearing-agent 
they  float  upon  the  surface  of  the  latter,  and  can  then  be  flattened 
and  all  folds  removed.  As  the  alcohol  is  extracted  the  sections 


430  HISTOLOGICAL   TECHNIQUE. 

sink  in  the  clearing-agent.  In  order  to  transfer  them  from  the 
clearing-agent  to  a  slide,  the  first  step  in  mounting,  a  good  method 
is  to  slip  a  strip  of  cigarette-paper  under  the  section,  withdraw  it 
along  with  the  section  (using  a  platinum  needle  as  aid,  if  necessary), 
drain  off  the  superfluous  fluid,  and  then  lay  the  cigarette-paper  on 
the  slide,  section  side  down.  Light  pressure  will  now  squeeze  out 
considerable  of  the  clearing-agent,  when  the  paper  can  be  stripped 
from  the  section  and  slide,  leaving  the  section  nearly  dry  and  with- 
out folds  or  wrinkles.  With  a  little  care,  this  method  of  transferring 
the  section  to  the  slide  rarely  fails.  When  such  is  the  case  the 
manipulations  must  be  repeated. 

A  drop  of  the  mounting-medium  is  now  placed  upon  the  section 
and  a  cover-glass  laid  on  and  gently  pressed  down  until  it  comes  in 
contact  with  the  section  and  the  excess  of  balsam  or  dammar  is 
expelled  from  beneath  the  cover.  If  the  sections  tend  to  raise  the 
cover,  the  latter  may  be  weighted  with  a  bullet  placed  in  its  centre. 
Freshly  mounted  specimens  are  not  so  favorable  for  examination 
with  high  powers  as  those  that  have  been  mounted  for  a  few  hours 
or  days.  This  is  because  the  refractive  indices  of  the  clearing-agent 
and  mounting-medium  are  not  identical.  When  these  have  become 
thoroughly  mixed,  or  the  former  has  evaporated,  the  specimen  is 
impregnated  with  and  surrounded  by  a  homogeneous  medium  that 
does  not  scatter  the  light  passing  through  it. 

Canada  balsam  has  a  somewhat  higher  refractive  index  than 
dammar.  It  therefore  renders  the  sections  a  little  more  transparent 
and  more  completely  obliterates  the  structure-picture.  When  it  is 
desired  to  retain  as  much  of  the  structure-picture  as  possible, 
which  is  usually  the  case,  dammar  should  be  chosen  for  the  mount- 
ing-medium. It  dries  a  little  more  slowly  than  balsam,  but  soon  is 
sufficiently  dry  at  the  edges  of  the  cover-glass  to  preserve  the  sec- 
tion from  injury.  If  the  slides  are  kept  in  a  horizontal  position, 
in  a  warm  place  (40°  to  50°  C. ;  104°  to  122°  F.),  for  a  couple  of 
days,  they  will  be  dry  enough  for  storage,  but  for  several  weeks 
must  be  handled  with  care. 

Stained  sections  may  be  examined  in  glycerin,  having  been 
mounted  by  the  same  manipulations  as  those  used  for  mounting 
in  balsam,  without  previous  dehydration  or  clearing.  Such  mounts 
are,  however,  difficult  of  preservation.  The  various  cements  that 
have  been  recommended  for  fastening  the  edges  of  the  cover-glass 
to  the  slide  are  usually  inefficient,  as  the  changes  of  temperature 


RAPID  PREPARATION  OF  SECTIONS  FOR  DIAGNOSIS.     431 

that  are  inevitable  cause  the  glycerin  to  make  its  way  between  the 
glass  and  cement,  loosening  the  latter. 

A  better  medium  than  glycerin  for  sections  that  cannot  be  sub- 
jected to  the  action  of  alcohol  for  the  purpose  of  dehydration  is 
glycerin-jelly.  This  is  prepared  by  soaking  the  best  French  gelatin 
in  cold  water  until  it  has  imbibed  all  it  will  readily  take  up,  then 
melting  the  gelatin,  after  pouring  off  the  excess  of  water,  and 
adding  an  equal  bulk  of  glycerin.  A  little  carbolic  acid  may  be 
added  to  the  mixture  to  preserve  it.  The  manipulations  for  mount- 
ing are  similar  to  those  given  above,  the  sections  being  transferred 
from  water  to  the  slide.  The  glycerin-jelly  may  be  melted  and  a 
drop  placed  upon  the  section,  or  a  little  lump  of  the  solid  jelly  may 
be  placed  upon  a  cover-glass,  melted  by  gentle  heat,  and  the  cover- 
glass  then  inverted  over  the  section  on  the  slide.  After  the  jelly 
has  dried  at  the  edges  of  the  cover-glass  they  may  be  painted  with 
xylol  balsam,  dammar,  or  some  cement. 

The  Rapid  Preparation  of  Sections  for  Diagnosis. 

The  most  expeditious  means  of  obtaining  sections  of  fresh  tis- 
sues is  to  cut  them  without  preliminary  treatment  with  reagents, 
either  free  hand  with  a  razor,  or  with  the  aid  of  a  freezing  mi- 
crotome (page  415).  Such  sections  may  be  stained  with  methylene- 
blue  (aqueous  solution,  page  423),  or  they  may  be  examined  in 
neutral  salt  solution.  If  they  are  to  be  stained,  spread  them  out 
on  a  slide,  pour  a  few  drops  of  the  methylene-blue  solution  over 
them,  and,  after  a  few  moments,  wash  off  the  dye  with  water  and 
cover  the  section.  If  such  rapid  work  is  not  necessary,  the  sections 
can  be  fixed  in  formalin  (page  416),  and,  after  washing  out  that 
reagent,  stained.  Such  sections  may  be  hardened  and  dehydrated, 
by  placing  them  in  dishes  of  increasingly  strong  alcohols,  and 
finally  mounted  in  dammar ;  but  the  results  are  by  no  means  so 
good  as  when  fixation  and  hardening  are  done  before  sections  are  cut. 

When  time  is  not  pressing  the  following  method  will  give  good 
results : 

1 .  Fix  and  harden  pieces  not  over  \  inch  thick  in  absolute  alcohol 
on  quick-lime  over  night  (page  407). 

2.  Dip  the  specimen  in  thick  collodion  and  embed  it  on  a  glass 
block  by  the  rapid  method  (page  412).    When  the  block  has  been  in 
80  per  cent,  alcohol  for  three  or  four  hours  it  may  be  cut ;  but  it  is 
better  to  let  the  collodion  harden  for  twenty-four  hours. 


432  HISTOLOGICAL  TECHNIQUE. 

3.  Stain  with  hsematoxylin  and  eosin  (page  418),  cutting  short  the 
time  of  washing  after  the  hsematoxylin,  if  in  a  hurry. 

4.  Dehydrate  in  95  per  cent,  alcohol ;  two  successive  baths. 

5.  Clear  in  carbol-xylol. 

6.  Mount  in  xylol-dammar. 

Very  serviceable  sections  can  be  prepared  in  less  than  twenty- 
four  hours  by  this  method,  and  the  specimens,  though  not  of  the 
best  quality,  will  be  permanent,  and  may  be  kept  for  future  refer- 
ence. 

Special  Methods. 

The  foregoing  methods  are  for  the  preparation  of  tissues  from 
which  sections  must  be  made  before  they  are  fit  for  examination 
under  the  microscope.  The  physician  is,  however,  frequently  called 
upon  to  examine  other  objects,  when  the  following  directions  will  be 
found  useful. 

1.  Examination  of  Urinary  and  other  Sediments. — For  the  collec- 
tion of  the  sediment  vessels  with  vertical  walls  should  be  used,  not 
conical  glasses.  A  test-tube  answers  very  well.  The  sediment 
should  be  allowed  to  settle  for  several  hours  in  a  cool  place,  to 
avoid  decomposition ;  or,  better,  the  sediment  should  be  precipitated 
by  means  of  a  centrifuge.  It  should  be  borne  in  mind  that  urine 
becomes  alkaline  during  decomposition,  and  that  the  ammonia  pro- 
duced causes  changes  in  the  characters  of  the  crystalline  or  other 
inorganic  constituents  of  the  sediment,  and  also  renders  the  identi- 
fication of  the  organic  constituents  difficult  or  impossible. 

When  the  sediment  has  collected  at  the  bottom  of  the  vessel  a 
portion  should  be  removed  with  a  pipette  for  examination.  Place 
the  finger  over  one  end  of  the  pipette  before  introducing  it  into 
the  liquid,  to  retain  the  air,  then  place  the  other  end  in  contact 
with  the  sediment  and  allow  the  air  to  escape  slowly  by  raising  or 
moving  the  finger  a  little.  Close  the  upper  end  of  the  pipette  and 
withdraw  it.  Now  carefully  wipe  the  outside  of  the  pipette  and  let 
the  fluid  escape  until  a  good  sample  of  the  sediment  is  at  the  end  of 
the  tube.  Place  a  drop  of  this  sediment  on  a  slide  arid  cover.  Ex- 
amine the  specimen  with  a  low  power  at  first,  taking  care  to  use  a 
very  small  diaphragm.  In  this  way  the  presence  of  urinary  casts 
may  be  more  rapidly  determined  than  if  a  high  power  is  used. 
When  there  is  doubt  as  to  a  given  object  being  a  cast  examine  it  with 
a  higher  power.  After  the  specimen  has  been  examined  for  casts 
and  other  objects  large  enough  to  be  identified  with  a  low  power, 


SPECIAL  METHODS.  433 

use  the  high  power  for  the  detection  of  red  blood-corpuscles,  pus, 
etc.  Objects  in  urinary  sediments  may  be  stained  with  aqueous 
methylene-blue,  Gram's  solution  of  iodine,  or  alum-carmine;  or 
their  chemical  nature  determined  by  means  of  microchemical  reac- 
tions. 

2.  Preparation  of    Cover-glass   Smears. — These  are  used  for  the 
examination  of  blood,  pus,  sputa,  cultures  of  bacteria,  etc.,  when  it 
is  desired  to  employ  stains.     They  are  also  employed  occasionally 
for  the  study  of  some  of  the  constituents  of  soft  tissues. 

A  small  drop,  or  fragment,  of  the  specimen  is  placed  between 
two  cover-glasses.  If  the  specimen  is  sufficiently  fluid,  it  will  at 
once  spread  out  into  a  thin  layer  between  the  covers.  When  this 
is  not  the  case  pressure  may  be  used.  The  covers  are  then  drawn 
apart,  not  lifted,  leaving  a  coating  upon  both.  They  are  allowed  to 
dry  spontaneously,  after  which  the  film  is  fixed  by  passing  the 
cover-glasses  three  times  through  a  flame,  care  being  taken  not  to 
scorch  the  film,  which  should  not  come  in  contact  with  the  flame. 
Heat  applied  through  the  glass  to  the  dry  film  will  render  it  insol- 
uble and  affix  it  to  the  cover.  The  constituents  of  the  film  may 
then  be  stained  on  the  cover-glass,  the  latter  being  either  floated 
on  the  dye  or  immersed  in  it  as  though  it  were  a  section.  Hsema- 
toxylin  and  eosin  may  be  employed ;  but  anilin-dyes,  such  as  meth- 
ylene-blue, carbol-fuchsin,  anilin-gentian- violet,  etc.,  are  more  com- 
monly used. 

3.  Examination  of  Sputa  for  Tubercle  Bacilli. — The  small  cheesy 
particles  in  the  sputa  are  most  likely  to  contain  tubercle  bacilli. 
Cover-glass  smears  are  stained  by  the  following  method  : 

a.  Stain  fifteen  minutes  in  freshly  filtered  carbol-fuchsin  at  the 
room-temperature,  or  heat  until  vapors  rise  from  the  surface  of  the 
dye,  and  maintain  that  temperature  for  about  three  minutes. 

6.  Wash  off  the  excess  of  dye  with  water. 

c.  Differentiate  in  dilute  sulphuric  acid,  prepared  by  adding  5  cc. 
of  pure  acid  to  95  cc.  of  distilled  water,  until  the  cover-glass  has 
only  a  faint  tinge  of  pink  when  the  acid  is  washed  off*  with  water. 

d.  Wash  in  water  to  remove  the  acid. 

e.  Counterstain  with  aqueous  methylene-blue  for  two  minutes. 
/.  Wash  in  water. 

g.  Dry  the  cover-glass  and  mount  it,  film  side  down,  on  a  drop 
of  xylol-dammar. 

The  tubercle  bacilli  will  be  stained  red,  while  other  bacteria  and* 

28 


434  HISTOLOGICAL   TECHNIQUE. 

the  nuclei  of  cells  will  be  blue.  This  method,  like  all  others  used 
for  the  detection  of  the  tubercle  bacillus,  depends  upon  the  fact  that 
that  bacillus  takes  up  colors  with  reluctance,  but,  after  staining, 
holds  them  tenaciously.  The  specimen  is  therefore  first  stained 
with  a  strong  dye,  is  then  decolorized  with  some  agent  that  will 
discharge  the  color  from  all  bacteria  except  the  tubercle  bacillus 
(and  spores,  which,  however,  have  a  different  shape  from  that  of 
the  tubercle  bacillus),  and  afterward  stained  with  a  weaker  dye  of 
another  color  which  is  imparted  to  the  bacteria  that  have  been 
decolorized. 

4.  Examination  of  Urethral  Pus  for  the  Gonococcus. — The  gono- 
coccus  is  shaped  a  little  like  a  coffee-bean,  and  usually  occurs  in 
pairs  with  the  flattened  surfaces  of  the  individual  cocci  facing  each 
other.     In  pus  it  is  frequently  situated  within  the  leucocytes,  while 
the  other  varieties  of  pyogenic  cocci  usually  lie  outside  of  the  pus- 
corpuscles.    The  gonococcus  is  decolorized  by  treatment  with  Gram's 
iodin  solution  followed  by  alcohol;  the  more  common  cocci  found 
in  suppuration  are  not  decolorized.     These  differences  in  shape,  sit- 
uation, and  behavior  toward  dyes  serve  to  distinguish  the  gonococci 
from  the  other  cocci  that  may  be  present.     The  smears,  fixed  by 
heat,  are  stained  as  follows : 

a.  Stain  for  five  minutes  in  freshly  filtered  anilin-gentian-violet. 
6.  Wash  off  excess  of  dye  with  water. 

c.  Immerse  in  Gram's  solution  for  two  minutes. 

d.  Decolorize  in  95  per  cent,  alcohol  till  no  more  color  is  given  off. 

e.  Stain  two  minutes  in  aqueous  fuchsin,  prepared  in  a  manner 
similar  to  that  used  for  aqueous  methylene-blue.     Bismarck-brown 
may  be  used  for  .this  counterstain  in  place  of  the  fuchsin. 

/.  Wash  in  water,  dry,  and  mount  in  dammar  or  balsam.  The 
gonococci  will  be  stained  by  the  second  dye  used ;  other  cocci  be- 
longing to  the  pyogenic  group  will  be  a  dark  purple,  they  having 
retained  the  color  first  imparted  to  all  the  bacteria  by  the  gentian- 
violet.  In  this  case  the  gonococci  are  distinguished  from  the  other 
cocci  by  taking  advantage  of  the  fact  that  they  are  "  negative  to 
Gram,"  while  the  others  are  "  positive." 

5.  Examination   of  Blood-smears. — Hsematoxylin,  followed   by  a 
strong  counterstain  with   eosin,  will  furnish  useful  specimens  for 
most  purposes.     The  differentiation  of  the  various  granules  in  the 
white  corpuscles  described  by  Ehrlich  requires  special  methods,  for 
a  description  of  which  the  reader  is  referred  to  special  works  on  the 


SPECIAL  METHODS.  435 

blood  or  clinical  microscopy.  The  malarial  plasmodia  are  best 
detected  in  perfectly  fresh  blood,  examined  immediately  with  an 
immersion-Ion;-:,  when  their  changes  of  form  serve  to  make  them 
more  easily  recognizable  than  when  they  are  sought  in  smears.  In 
the  latter  they  may  be  stained  by  the  following  method  : 

a.  Fix  the  film  by  means  of  heat,  or,  better,  by  immersion  in 
absolute  alcohol  for  half  an  hour.  (In  the  latter  case  wash  off  the 
alcohol  with  water  before  staining.) 

6.  Stain  for  several  hours  in  Chenzinsky-Pehn's  stain : 

Concentrated  alcoholic  solution  of  methylene-blue,  10  cc. 
0.5  per  cent,  solution  of  eosin  in  70  per  cent,  alcohol,  5  cc. 
Distilled  water,  10  cc. 

The  solution  should  be  filtered  before,  and  preserved  from  evap- 
oration during,  the  staining. 

c.  Wash  in  water,  dry,  mount  in  xylol-dammar. 

The  malarial  plasmodia  will  be  stained  blue,  the  body  of  the  red 
corpuscles  red,  the  nuclei  of  the  leucocytes  blue,  and  eosinophile 
granules,  within  those  cells,  red. 

6.  Examination  of  Bacteria  in  Cover-glass  Preparations. — If  the  bac- 
teria are  already  in  a  fluid,  a  drop  is  placed  upon  a  cover-glass,  spread 
over  its  surface,  allowed  to  dry  spontaneously,  and  then  fixed  by  heat, 
as  described  above.     If  cultures  on  solid  media  are  to  be  examined, 
a  drop  of  water  is  first  placed  upon  the  cover-glass,  and  a  little 
mass  of  the  bacteria  disseminated  through  it,  and  then  the  mixture 
is  spread  in  a  thin  layer  by  means  of  the  platinum  needle.     It  is 
then  dried  and  fixed,  as  in  the  preceding  case.     Such  preparations 
may  be    stained   with  methylene-blue,   carbol-fuchsin,   by  Gram's 
method   (anilin-gentian-violet,  followed  by  Gram's  iodine  solution, 
and  then  alcohol),  or  with  some  other  anilin-dye.     For  the  diph- 
tlierin    or  typhoid  bacillus  an  alkaline  methylene-blue  (see  Unna's 
formula)  serves  well. 

7.  Examination  in  Hanging  Drop. — This  method  is  useful  for  the 
observation  of  objects  suspended  in  a  fluid.     It  is  extensively  used 
in  bacteriology   fur  the  study  of  living  bacteria.     A  drop  of  the 
fluid  is  placed  on  the  centre  of  a  cover-glass,  which  is  then  inverted 
over  the  concavity  in  a  hollowed  slide.     'Flic  edges  of  the  cover- 
glass  should  then  he  sealed  with  a  drop  of  water  or  oil,  to  prevent 
evaporation  of  the  hanging  drop. 


436  HISTOLOGICAL   TECHNIQUE. 

8.  Microchemical  Reactions. — These  reactions  are  resorted  to  to 
determine  the  chemical  nature  of  objects  under  the  microscope. 
Every  stain  is  the  result  of  a  microchemical  reaction,  but  as  yet 
the  knowledge  obtained  by  staining  tissues  cannot  always  be  ex- 
pressed in  chemical  language. 

The  manipulations  are  usually  so  conducted  that  the  reaction  can 
be  directly  observed  under  the  microscope.  The  object  to  be  studied 
is  placed  in  the  middle  of  the  field.  The  reagent  used  is  then 
placed  at  one  edge  of  the  cover-glass,  whence  some  of  it  will  flow 
beneath  the  latter.  To  facilitate  the  entrance  of  the  reagent  a  nar- 
row strip  of  filter-paper  may  be  brought  in  contact  with  the  oppo- 
site edge  of  the  cover,  withdrawing  some  of  the  fluid  from  beneath 
it.  It  is  best  to  sharpen  the  end  of  the  strip  which  comes  in  con- 
tact with  the  cover-glass,  so  that  the  •  absorption  of  fluid  shall  be 
slow;  otherwise  the  currents  induced  will  be  likely  to  wash  the 
object  from  the  field  of  vision.  The  following  tests,  applied  in  this 
way,  may  be  of  use : 

a.  Urates.     Insoluble  in  1  per  cent,  acetic  acid ;  soluble,  on  the 
application  of  heat,  in  water  (or  urine).    The  slide  must  be  removed 
from  the  microscope  when  heat  is  applied  to  it. 

b.  Earthy  phosphates.     Dissolve  on  the  addition  of  1  per  cent, 
acetic  acid.     Are  not  dissolved  by  heat. 

c.  Calcium  oxalate.     Insoluble  in  1  per  cent,  acetic  acid  ;  soluble 
in  1  per  cent,  hydrochloric  acid. 

d.  Carbonates.    Soluble  in  1  per  cent,  acetic  acid  or  hydrochloric 
acid,  with  evolution  of  gas-bubbles. 

e.  Albuminoid  granules.    Become  indistinct,  and  finally  invisible, 
on  the  addition  of  1  per  cent,  acetic  acid  or  1  per  cent,  potassium 
hydrate ;  not  blackened  by  osmic  acid. 

/.  Fatty  granules.  Not  affected  by  1  per  cent,  acetic  acid  or  1 
per  cent,  potassium  hydrate.  Stained  black  or  dark  brown  by  osmic 
acid. 

g.  Starch.  Stained  dark  blue  to  black  by  iodine  solutions.  Use 
Gram's  solution. 

h.  Cellulose.  Stained  yellow  by  iodine  solutions.  If  the  water 
be  then  removed  and  concentrated  sulphuric  acid  introduced,  the 
color  becomes  blue.  The  walls  of  most  vegetable  cells  are  composed 
of  cellulose. 

i.  Teichmann's  test  for  haemoglobin.  This  test  depends  upon  the 
conversion  of  the  haemoglobin  or  its  derivatives  into  hsemin,  which 


SPECIAL  METHODS.  437 

crystallizes  in  rhombic  plates  of  a  reddish-brown  color.  The  haemin 
is  produced  by  heating  with  a  little  salt  and  strong  acetic  acid. 
Evaporate  a  drop  of  neutral  salt  solution  to  dryness  on  a  slide. 
Place  the  substance  to  be  tested  upon  it  and  cover.  Fill  the  space 
between  cover  and  slide  with  glacial  acetic  acid  and  heat  over  a 
flame  till  bubbles  begin  to  form.  Maintain  that  heat  for  a  few 
minutes,  replacing  loss  by  fresh  additions  of  acetic  acid.  Let  the 
slide  cool  slowly,  and,  when  cold,  examine.  If  the  results  are  nega- 
tive, repeat  the  heating  with  acetic  acid.  The  acid  should  not 
actually  boil,  but  should  be  kept  at  the  point  of  incipient  ebullition. 

j.  Tests  for  amyloid  substance.  Sections  of  fresh  tissue  may  be 
soaked  for  some  time  in  Gram's  solution,  then  washed  and  examined 
in  water.  Amyloid  substance  is  stained  reddish-brown,  the  tissues 
yellow.  Sections  of  tissues  fixed  in  alcohol,  corrosive  sublimate,  or 
formaldehyde,  may  be  stained  in  a  solution  of  1  per  cent,  methyl- 
violet  dissolved  in  distilled  water,  without  the  addition  of  alcohol. 
The  sections  are  then  washed  in  1  per  cent,  hydrochloric  acid  for 
the  purpose  of  differentiating  the  stain.  After  thorough  washing 
in  several  changes  of  water  they  may  be  mounted  in  glycerin-jelly. 
The  amyloid  substance  is  stained  reddish-violet,  the  other  tissues 
blue. 

k.  Test  for  iron  in  pigmentations.  The  iron  from  the  haemo- 
globin of  the  blood  is  sometimes  present  in  the  pigmentation  result- 
ing from  old  extravasations,  in  the  form  of  hsemosiderin.  The 
same  compound  is  also  sometimes  found  in  the  tissues  in  cases  of 
pernicious  anaemia.  The  presence  of  iron  in  this  pigmentation  may 
be  demonstrated  by  the  following  method  : 

(a)  The  tissues  should  be  fixed  in  alcohol. 

(6)  Soak  the  section  in  a  2  per  cent,  solution  of  potassium  ferro- 
cyanide  for  ten  minutes. 

(c)  Transfer  to  Orth's  acid  alcohol  (page  422)  for  five  or  ten 
minutes. 

The  sections  may  now  be  examined  in  a  glycerin-mount  with  a 
wide  diaphragm,  or  they  may  be  counterstained,  for  which  purpose 
treat  as  follows : 

(d)  Wash  with  water. 

(e)  Stain  with  Orth's  lithio-carmine. 

(/)  Dehydrate  and  mount  in  xylol-dammar. 
The  iron  in  the  section  is  converted  into  Prussian  blue  ;  the  nuclei 
of  the  cells,  when  the  counterstain  has  been  employed,  are  red. 


438  HISTOLOGICAL   TECHNIQUE. 

I.  Examination  of  sputa  for  elastic  fibres.  In  pulmonary  disease 
involving  a  destruction  of  pulmonary  tissue  and  the  appearance  of 
fragments  in  the  expectoration,  elastic  fibres  from  the  alveolar  walls 
may  frequently  be  found  in  the  sputa : 

Fill  a  test-tube  one-third  full  of  sputa,  add  five  or  six  drops  of 
36  per  cent,  potassium  hydrate  solution,  and  boil  the  mixture  for 
three  or  four  minutes.  Add  an  equal  bulk  of  distilled  water. 
Divide  the  contents  of  the  tube  between  the  two  tubes  of  the  cen- 
trifuge and  precipitate  their  contents.  If  elastic  fibres  Avere  pres- 
ent, they  will  be  found  either  in  the  sediment  or  in  the  scum  on  the 
top  of  the  fluid. 

9.  Methods  of  Maceration. — 

a.  One-third  alcohol. 

95  per  cent,  alcohol,  35  cc. 

Distilled  water,  65  " 

This  dilute  alcohol  is  excellent  for  the  separation  of  epithelium 
from  the  surfaces  of  mucous  membranes.  The  fresh  tissues  are 
placed  in  the  alcohol  for  a  day  or  two,  after  which  the  cells  can 
easily  be  detached  and  separated  by  shaking.  The  cells  are  well 
preserved,  and  may  be  stained  with  methylene-blue  or  alum-car- 
mine. 

b.  Potassium  hydrate. 

Potassium  hydrate,  pure  by  alcohol,  36  grams. 

Distilled  water,  64  cc. 

The  solution  should  be  cold  before  use.  It  cannot  be  filtered 
through  paper ;  but  if  not  clear,  should  be  decanted  from  any  sedi- 
ment, or  a  fresh  solution  prepared.  Maceration  takes  place  very 
quickly  in  this  solution.  The  tissues  can  usually  be  teased  apart 
within  fifteen  to  thirty  minutes.  They  must  be  examined  in  the 
potash  solution  without  dilution,  as  the  addition  of  water  quickly 
destroys  the  tissue-elements.  For  this  reason  the  specimens  to  be 
macerated  should  be  placed  in  several  times  their  bulk  of  the  pot- 
ash solution  ;  otherwise  the  water  they  contain  will  dilute  the  pot- 
ash. Permanent  mounts  cannot  be  made. 

c.  Chromic  acid.     A   solution  of   1  part  of  the  acid   in  10,000 
parts  of  distilled  water  will  facilitate  the  teasing  apart  of  tissue- 
elements  which  have  macerated  in  it  for  one  to  several  days.    After 
careful  washing  on  the  slide  alum-carmine  alone,  or  followed  by 
picric  acid,  may  be  used  for  staining. 


SPECIAL  METHODS:  439 

10.  Methods  of  Decalcification. — Tissues  which  contain  calcified 
nodules  or  bone  must  be  freed  from  lime-salts  before  they  can  be 
cut.  It  is  difficult  to  do  this  rapidly  without  injury  to  the  softer 
tissue-elements.  When  good  results  are  desired,  and  the  necessary 
time  can  be  afforded,  the  tissues  should  first  be  fixed  and  hardened, 
small  pieces  being  selected.  Zenker's  fluid  fixes  wrell  for  this  pur- 
pose, but  Orth's  fluid  or  alcohol  may  be  used.  If  Zenker's  or  Orth's 
fluid  is  used,  the  tissues  must  be  washed  in  water  and  hardened  in 
alcohol  for  at  least  a  day  before  they  are  decalcified  (see  Methods  of 
Fixing  and  Hardening,  pp.  403,  408). 

Decalcification  is  accomplished  by  treatment  with  acids.  Five 
per  cent,  nitric  acid  will  decalcify  small  pieces  of  bone  in  from  one 
to  five  days.  The  progress  of  the  decalcification  may  be  deter- 
mined by  pricking  the  tissue  with  a  needle,  but  after  it  appears 
to  be  soft  it  is  well  to  continue  the  action  of  the  acid  for  a  day  or 
two,  lest  some  undissolved  particles  should  remain  and  injure  the 
edge  of  the  microtome-knife.  A  saturated  aqueous  solution  of 
picric  acid  is  sometimes  used  for  decalcifying.  Its  action  is  very 
slow,  though  not  injurious  to  the  tissues,  which  require  no  prelimi- 
nary treatment,  the  picric  acid  acting  as  a  fixing  and  decalcifying 
agent. 

After  decalcifying  in  nitric  acid  the  tissues  should  be  thoroughly 
washed  in  running  water  for  twenty-four  hours  and  then  rehardened 
in  alcohol,  after  which  they  may  be  embedded.  After  decalcifying 
in  picric  acid  the  tissues  are  placed  in  70  per  cent,  alcohol  and  hard- 
ened without  previous  washing  in  water. 

When  rapid  decalcification  is  necessary  nitric  acid  and  phloro- 
glucin,  which  restrains  the  destructive  action  of  the  acid,  may  be 
used.  The  solution  is  prepared  by  dissolving  1  gram  of  phloro- 
glucin  in  10  cc.  of  pure  nitric  acid.  To  this  100  cc.  of  10  per  cent, 
nitric  acid  are  added.  Decalcification  takes  place  within  a  few  hours 
in  this  solution,  which  contains  about  20  per  cent,  of  nitric  acid. 
The  tissues  should  then  be  washed  and  hardened. 

Another  rapid  method  which  combines  decalcification  with  hard- 
ening is  to  place  the  fresh  tissues  in  a  large  bulk  of  5  per  cent, 
nitric  acid  in  80  per  cent,  alcohol.  After  decalcification  has  taken 
place  the  tissues  are  hardened  in  alcohols  of  increasing  strength, 
large  quantities  being  used  in  order  to  remove  the  acid.  Before 
staining,  the  sections  should  be  washed  thoroughly  in  water  to  get 
rid  of  any  residual  traces  of  acid. 


INDEX. 


A  BSCESS,  312 

A  cold,  319 
Absorption,  295 
Achromatin,  34 
Acidophilic  cells,  119 
Active  hyperaemia,  298 
Acute  inflammation,  297 

parenchymatous  inflammation,  268 

nephritis,  272 
Adeno-carcinoma,  390 
Adeno-fibroma,  377 
Adenoma,  376 
Adipose  tissue,  78 
Adrenal  bodies,  186 
Adventitia,  112 
Akromegaly,  191 
Albumin,  Mayer's,  417 
Albuminoid  degeneration,  266 
Alcohol,  absolute,  407 
Alveoli,  pulmonary,  171 
Amoeba,  28 
Amyloid  infiltration,  281 

substance,  tests  for,  437 
Anaemic  infarcts,  332 
Angiomata,  373 
Angiomatous  tumors,  373 
Anilin-water,  424 
Areolar  tissue,  76 
Arteries,  110 

helicine,  223 
Association-fibres  of  cerebrum,  249 

of  spinal  cord,  239 
Atrophy,  284 

functional,  284  , 

pressure-,  285 

senile,  287 

Attraction-spheres,  35 
Axis-cylinder,  97 

BACTERIA,  examination  of,  435 
Basement-membrane,  58 
Basophilic  leucocytes,  126 
Bergamot,  oil  of,  429 
Bladder,  164 
Blood,  122 

-plates,  126 

-smears,  preparation  of,  434 
Bodies,  adrenal,  186 

Malpighian,  154 


Bodies,  Malpighian,  of  spleen,  177 

Pacinian,  252 

pearl-,  390 

polar,  35,  217 
Body,  pituitary,  139 
Bone,  68 

canaliculi  of,  68 

general  character  of,  68 

Haversian  canals  of,  68 

lacunae  of,  68 

-marrow,  71,  119 
red,  119 
yellow,  119 

regeneration  of,  338 
Bowman,  glands  of,  255 
Bowman's  capsule,  159 
Bronchi,  169 
Bronchioles,  170 
Broncho-pneumonia,  317 
Brownian  movement,  29 
Brunner,  glands  of,  141 
Bulb,  olfactory,  258 
glomeruli  of,  257 

pACHEXIA  strumipriva,  183 
\J    Calcareous  infiltration,  282 
Calcium  oxalate,  tests  for,  436 
Callus,  309 

Canada-balsam,  428, 430 
Capillaries,  113 
Capsule,  Bowman's,  159 

Glisson's,  146 
Capsules,  supra-renal,  186 
Carbol-fuchsin,  423 
Carbonates,  tests  for,  436 
Carbo-xylol,  429 
Carcinoma,  382 

colloid,  388 

medullary,  384 

scirrhous,  384 

simple,  384 
Cardiac  glands,  136 

muscles,  89 
Carmine,  alum-,  421 

borax-,  421 

lithio-,  422 

neutral,  420 
Carotid  glands,  194 
Curtilage,  64 

441 


442 


INDEX. 


Cartilage,  elastic,  67 

fibro-,  66 

general  character  of,  64 

hyaline,  66 

matrix  of,  65 

ossification  of,  64 

regeneration  of,  338 
Catarrhal  inflammations,  316 

pneumonia,  317 
Cedar-wood,  oil  of,  429 
Cell,  or  cells,  27 

acidophilic,  119 

compound  granule-,  316 

decidual,  215 

of  Deiters,  260 

-division,  40 
amitotic,  40 
centrosome  in,  34 

ganglion-,  95 

giant-,  40,  119 

glia-,  101 

goblet-,  52,  139 

hair-,  260 

migratory,  124 

mitral,  258 

of  Miiller,  262 

nerve-,  95 

organs  of,  31 

plasma-,  120 

prickle-,  55 

of  Purkinje,  243 

reproduction  of,  34 

of  Sertoli,  225 

stellate,  245 

sustentacular,  of  retina,  261 
in  testis,  227 

wandering,  124 
Cellulose,  tests  for,  436 
Centrosome,  31 
Cerebellum,  243 
Cerebrum,  246 

association-fibres  of,  250 

commissure-fibres  of,  249 

projection-fibres  of,  249 
Cheesy  degeneration,  274 
Chemotactic  substances,  309 
Chemotaxis,  309 
Chondroma,  350 
Chromatin,  34 

reduction  of,  226 
Chromolysis,  294 
Chromoplasm,  34 
Chromosomes,  37 
Chronic  inflammations,  322 
interstitial,  324 
parenchymatous,  269 
Chyle,  126 

Cicatricial  tissue,  308 
Ciliated  epithelium,  53 
Circulatory  system,  108 
Cirrhosis  of  liver,  323 
Clarke,  column  of,  241 
Clearing,  methods  of,  428 


Clearing,  methods  of,  bergamot,  oil  of,  429 
carbol-xylol,  429 
cedar-wood,  oil  of,  429 
cloves,  oil  of,  429 
origanum,  oil  of,  429 
xylol,  428 

Clefts  of  Lantermann,  99 
Cloves,  oil  of,  429 
Coagulation,  explanation  of,  127 

-necrosis,  294 
Coccygeal  gland,  195 
Collateral  fibres  of  spinal  cord,  239 
Colliquative  necrosis,  295 
Collodion,  409,  412 
Colloid,  181 

carcinoma,  388 

degeneration,  278 
Colon,  142 
Colostrum,  219 

-corpuscles,  219 
Column  of  Clarke,  241 
Columnar  epithelium,  52 
Commissure-fibres  of  cerebrum,  249 
Compensatory  hypertrophy,  289 
Congestion,  passive,  326 
Connective  tissue,  63 

tumors,  347 

Contractile  substance,  83 
Cord,  spinal,  236 
Corium,  196 
Corpora  amylacea,  224 
Corpus  album,  210 

cavernosum,  222 

hsemorrhagicum,  210 

luteum,  210 

spongiosum,  222 
Corpuscles,  colostrum-,  219 

genital,  253 

of  Krause,  253 

of  Meissner,  253 

red,  123 

tactile,  252 

white,  124 
Croupous  inflammation,  317 

membrane,  319 
Crypts  of  Lieberkiihn,  139 
Cubical  epithelium,  49 
Cuticle  of  epithelium,  50 
Cuticularized  epithelium,  54 
Cutting,  methods  of,  415 
free-hand,  415 
frozen  sections,  415 
celloidin  sections,  416 
collodion  sections,  416 
Cylindroma,  356 
Cystoma,  392 
Cytoplasm,  29,  32 

r\ECALCIFICATION,  methods  of,  439 
\J     Decidual  cells,  215 
Degenerations,  265 

albuminoid,  266 

cheesy,  274 


INDEX. 


443 


Degenerations,  colloid,  278 

fatty,  266 

hyaline,  280 

keratoid,  280 

mucous,  277 

of  nerves,  283 

parenchymatous,  266 
Dehydration,  methods  of,  428 
Deiters'  cells,  260 
Dendrite,  234 
Dermoid  cysts,  392 
Developmental  hypertrophy,  230 
Diapedesis,  301 

Diaster-phase  of  karyokinesis,  38 
Digestive  organs,  128 
Diphtheritic  inflammation,  318 

membrane,  294 
Discus  proligerus,  209 
Dispirem-phase  of  knryokinesis,  38 
Ductless  glands,  62,  180 
Duodenum,  137 

"ECTODERM,  20 
LA  Ectoplasm,  29 
Elastic  cartilage,  67 

fibres,  73 
Eleidin,  198 
Elements,  sarcous,  93 
Elementary  tissues,  41 
Embedding,  methods  of,  411 
celloidin,  412 
collodion,  412 
paraffin,  413 
Embolism,  330 
Embryonic  layers,  22 
Encapsulation,  296 
Endoderm,  20 
Endoneurium,  100 
Endoplasm.  29 
Endothelioma,  355 
Endothelium,  45 

functions  of,  48 

general  characters  of,  45 

regeneration  of,  336 
Energy,  kinetic,  18 

potential,  18 
Eosin,  420 

Eosinophilic  leucocytes,  126 
Epicardium,  109 
Epidermis,  197 
Epididymis,  225 
Epiglottis,  168 
Epineurium,  100 
Epithelial  tumors,  376 
Epithelioma,  391 
Epithelium,  49 

ciliated,  53 

columnar,  52 

cubical,  49 

cuticle  of,  50 

cuticularized,  54 

functions  of,  41,  57 
activities  of,  57 


Epithelium,  general  characters  of,  49 

germinal,  '207 

glandular,  50 

pavement-,  51 

regeneration  of,  336 

stratified,  54 

transitional,  56 
Erectile  tissue,  222 
Erythroblasts,  119 
External  genitals,  217 
Exudate,  inflammatory,  301 

TULLOPIAN  tubes,  210 
D      Fatty  degeneration,  266 

infiltration,  574 
Fibres,  association-,  of  cerebrum,  250 

of  cord,  239 
collateral,  of  cord,  239 
commissure-,  of  cerebrum,  249 
connective-tissue,  staining,  425 
elastic,  73 
moss-,  246 
nerve-,  96 

staining,  426 

projection-,  of  cerebrum,  249 
Sharpey's,  70 
white,  73 
yellow,  73 
Fibrin,  126 

Fibrinous  inflammation,  313 
Fibro-cartilage,  66 
Fibroma,  347 
Fibrous  tissues,  general  character  of,  72 

regeneration  of,  336 
Figures,  mitotic,  preservation  of,  406 
Fixation,  methods  of,  403 
alcohol,  absolute,  407 
boiling,  408 

Flemming's  solution,  406 
formaldehyde,  405 
mercuric  chloride  solution,  405 
Miiller's  fluid,  403 
Orth's  fluid,  404 
Zenker's  fluid,  404 
Flemming's  solution,  406 
Follicles,  Graafian,  207 

lymph-,  143 
Formaldehyde,  405 
Fractures,  healing  of,  308 
Functional  atrophy,  284 
hypertrophy,  288 

f<ALL-BLADDER,  151 
\J    Ganglion-cells,  95,  234 
Gangrene,  296 

dry,  296 

moist,  296 

<  Jfiiital  corpuscles,  253 
Gentian-violet,  423 
Germinal  epithelium  of  ovary,  207 
Giant-cell  sarcoma,  367 
(limit-cells,  40,  119 
Gianuzzi,  crescents  of,  131 


444 


INDEX. 


Gland,  mammary,  218 

thyroid,  181 
Glands  of  Bowman,  255 

of  Brunner,  141 

cardiac,  of  stomach,  136 

carotid,  194 

coccygeal,  195 

ductless,  62,  180 

lymphatic,  114 

parotid,  131 

pyloric,  136 

salivary,  131 

sebaceous,  201 

secreting,  58 

sublingual,  131 

submaxillary,  131 

sweat-,  198 

Glandular  epithelium,  50 
Glioma,  394 
Glisson's  capsule,  1 46 
Glomeruli,  olfactory,  258 
Glomerulus,  158 
Glycerin,  430 

jelly,  431 

Glycogenic  infiltration,  275 
Goblet-cells,  52,  139 
Gonococcus,  staining  of  the,  434 
Graafian  follicles,  207 

development  of,  208 
Gram's  solution,  424 
Granulation-tissue,  304 
Granules,  albuminoid,  tests  for,  436 

fatty,  tests  for,  436 
Granulomata,  318 

TT^EMANGIOMA,  374 
II     Hsematoidin,  328 
Haematoxylin,  418 
Haemoglobin,  tests  for,  436 
Haemorrhage,  328 
Hsemosiderin,  32$ 
Hair,  199 

-cells,  260 

cuticle  of,  200 

-follicles,  199 

development  of,  204 
Hanging-drop  preparations,  435 
Hardening,  methods  of,  408 
Haversian  canals,  68 
Hearing,  259 
Heart,  109 

Helicine  arteries,  223 
Henle,  tubes  of,  155 
Hepatization  of  lung,  gray,  313 

red,  313 
Hyaline  cartilage,  66 

degeneration,  280 
Hyaloplasm,  29 
Hyperaemia,  active,  298 

inflammatory,  298 

passive,  286,  326 
Hyperplasia,  288 

inflammatory,  290 


Hypertrophy,  288 

compensatory,  289 

developmental,  290 

functional,  288 

inflammatory,  290 
Hypophysis  cerebri,  189 

TMPEEGNATION,  methods  of,  409 
1      celloidin,  409 
collodion,  409 
paraffin,  409 
Infarcts,  332 

anaemic,  332 

haemorrhagic,  332 
Infiltration,  amyloid,  281 

calcareous,  282 

fatty,  274 

glycogenic,  275 

serous,  276 
Infiltrations,  265 
Inflammation,  acute,  297 
parenchymatous,  268 

catarrh  al,  316 

chronic,  322 
interstitial,  324 
parenchymatous,  269 

croupous,  317 

diphtheritic,  318 

fibrinous,  313 

serous,  315 
Inflammatory  exudate,  301 

hypersemia,  298 

hyperplasia,  290 

hypertrophy,  290 

repair,  303 

stasis,  298 

Infundibula  of  lung,  171 
Interstitium,  106 
Intestine,  small,  141 
Intima,  110 

Involuntary  muscles,  88,  91 
Iron-hematoxylin  stain,  425 

tests  for,  437 

T7AKYOKINESIS,  34 
IV     diaster-phase,  38 

dispirem-phase,  38 

monaster-phase,  37 

significance  of,  39 

spirem-phase,  35 
Karyolysis,  294 
Keloid,  360 
Keratin,  198 

Keratoid  degeneration,  280 
Kidney,  cortex  of,  153 

pelvis  of,  163 

Malpighian  bodies  of,  154 
Kidneys,  153 
Kinetic  energy,  18 
Krause,  corpuscles  of,  253 

T  ACTEALS,  114 

Jj     Lantermann,  clefts  of,  99 


INDEX. 


445 


Larynx,  168 
Layers,  embryonic,  22 
Leiomyoma,  370 
Leucocytes,  124 

basophilic,  126 

emigration  of,  300 

eosinophilic,  126 

large  mononuclear.  125 

pol ynuclear  neutrophilic,  ]  25 
Lieberkiihn,  crypts  of,  139 
Lipoma,  350 
Liver,  146 

cirrhosis  of,  323 

functions  of,  151 

lobules  of,  147 
Lobar  pneumonia,  313    - 
Lung,  functions  of,  173 
v    gray  hepatization  of,  313 

infundibula  of,  171 
v  red  hepatization  of,  313 
Lymph,  122 

-nodes,  114 

Lymphadenoid  tissue,  76 
Lymphatic  glands,  114 
Lymphatics,  114 
Lympho-angioma,  376 
Lymphocytes,  125 
Lympho-sarcoma,  363 

MACERATION,  methods  of,  438 
alcohol,  438 
chromic  acid,  438 
potassium  hydrate,  438 
Malpighian  bodies  of  kidney,  154 

bodies  of  spleen,  177 
Mammary  gland,  218 
Marrow,  71,  119 
Matrix  of  cartilage,  65 
Maturation  of  the  ovum,  217 
Mayer's  albumin,  417 
Measurements,  microscopical,  398 
Medullary  carcinoma,  384 

sheath,  97 

Meissner,  corpuscles  of,  253 
Melano-sarcoma,  369 
Membrane,  basement,  58 

cronpous,  318 

diphtheritic,  294 

pyogenic,  313 

Mercuric  chloride  solution,  405 
Mesoderm,  22 
Metakinesis,  37 
Metaplasia,  291 
Metaplasm,  33 
Methylene-blue,  aqueous,  423 

Unna's,  422 

Microchemical  reactions,  436 
Microscope,  care  of,  397 

selection  of,  397 
Microscopical  measurements,  398 

technique,  399 
Migratory  cells,  124 
Mitral  cells,  258 


Monaster-phase  of  karyokinesis,  37 
Mononuclear  leucocytes,  large,  125 
Moss-fibres,  246 
Motor  plates,  104 
Mounting,  methods  of,  429 
Canada-balsam,  428,  430 
Dammar,  428 
glycerin,  430 
glycerin-jelly,  431 
Movement,  Brownian,  29 

amoeboid,  29 
Mucoid  marrow,  119 
Mucous  degeneration,  277 

tissue,  74 
Mucus,  278 
Miiller,  cells  of,  262 
Miiller's  fluid,  403 
Muscular  tissues,  83 

tumors,  370 
Muscle,  cardiac,  89 

regeneration  of,  340 
involuntary,  88,  91 
smooth,  83 
function  of,  88 
regeneration  of,  339 
striated,  91 

regeneration  of,  340 
Myelin,  97,  98 
Myelocytes,  119 
Myxoedema,  183 
Myxoma,  353 

NAILS,  201 
Necrosis,  293 
coagulation-,  294 
liquefaction,  295 
of  nucleus,  294 

Nephritis,  acute  parencbymatous,  272 
Nerve-cells,  95 
degeneration  of,  283 
-fibres,  96 
-terminations,  103 
Nervous  system,  234 
tissues,  94 

regeneration  of,  340 
Neurilemma,  97 
Neurite,  234 
Neuroglia,  101 
Neurons,  234 
Nodes  of  Eanvier,  98 
Nucleolus,  29,  33 
Nucleus,  29 
necrosis  of,  294 
structure  of,  33 


rnsoPHAGUS,  134 

UJ  Olfactory  bulb,  258 

layers  of,  258 
glomeruli,  258 
Organs,  106 
Orth's  fluid,  404 
Origanum,  oil  of,  429 
Ossification  of  cartilage,  64 


446 


INDEX. 


Osteoma,  353 
Ovary,  207 
Ovula  Nabothi,  216 
Ovum,  20 

maturation  of,  217 

DACINIAN  bodies,  252 
JT   Pancreas,  142 
Papilloma,  394 
Paraffin,  409,  413 
Parathyroids,  185 
Parenchyma,  106 
Parenchymatous  degeneration,  266 

inflammation,  acute,  268 
chronic;  269 

nephritis,  acute,  272 
Passages,  alveolar,  170 
Passive  congestion,  326 

hypersemia,  326 
Pavement-epithelium,  51 
Pelvis,  renal,  163 
Penis,  222 
Perichondrium,  65 
Perineurium,  100 
Periosteum,  71 
Peyer's  patches,  143 
Phagocytosis,  332 
Phosphates,  earthy,  tests  for,  436 
Pia  mater,  251 
Picture,  color-,  402 

structure-,  402 
Pituitary  body,  189 
Plasma-cells,  120 
Pleurisy,  314 
Pneumonia,  broncho-,  317 

catarrh  al,  317 

lobar,  313 

Polar  bodies,  35,  217 
Polynuclear  neutrophilic  leucocytes,  1 25 
Potential  energy,  18 
Pressure-atrophy,  285 
Prickle-cells,  55 

Projection-fibres  of  cerebrum,  249 
Prostate,  224 
Protoplasm,  29 
Psammoma,  356 
Pseudopodium,  29 
Pseudo-stomata,  47 
Pulmonary  alveoli,  171 
Purkinje,  cells  of,  243 
Pus,  312 

Pyloric  glands,  136 
Pyogenic  membrane,  313 

RANVIER,  nodes  of,  98 
Razor,  stropping,  415 
Reaction,  microchemical,  436 
Rectum,  142 
Red  corpuscles,  123 
Regeneration  of  bone,  338 
of  cartilage,  338 
of  endothelium,  336 
of  epithelium,  336 


Regeneration  of  fibrous  tissue,  336 

of  muscles,  cardiac,  340 
smooth,  339 
striated,  340 

of  nervous  tissues,  340 

of  tissues,  334 
Renal  pelvis,  163 
Repair,  inflammatory,  303 
Reproductive  organs,  207 
Respiratory  organs,  168 
Rete  mucosum,  197 

vasculosum,  233 
Reticular  tissue,  76 
Retina,  260 

sustentacular  cells  of,  261 
Rhabdomyoma,  372 
Round-cell  sarcoma,  large,  364 
small,  362 

O  ALIVARY  glands,  131 
O  Salt  solution,  normal,  399 
Sarcolemma,  93 
Sarcoma,  359 

giant-cell,  367 

large  round-cell,  364 

lympho-,  363 

melanotic,  369 

small  round-cell,  362 

spindle-cell,  365 
Sarcoplasm,  93 
Sarcostyles,  93 
Sarcous  elements,  93 
Scar,  308 

Schwann,  sheath  of,  98 
Scirrhous  carcinoma,  384 
Sebaceous  glands,  201 
Secreting  glands,  58 
Secretion,  internal,  62 
Sections,  rapid  preparation  of,  431 

staining  of,  402 
Sediments,  examination  of,  432 
Seminal  vesicles,  225 
Senile  atrophy,  287 
Serous  infiltration,  276 

inflammations,  315 
Sertoli,  cells  of,  228 
Sharpey's  fibres,  70 
Sheath  of  Schwann,  98 
Sight,  260 

Simple  carcinoma,  384 
Skin,  196 

functions  of.  203 
Smears,  cover-glass,  433,  435 
Smell,  255 
smooth  muscles,  83 
Special  senses,  organs  of,  252 
spermatids,  227 
Spermatocytes,  227 
permatogonia,  227 
Spermatozoa,  231 
Spinal  cord,  236 

association-fibres  of,  239 
collateral  fibres  of,  239 


INDEX. 


447 


Spindle,  achromatic,  37 

Spindle-cell  sarcoma,  365 

Spirem,  formation  of,  35 

Spirem-phase  of  karyokinesis,  35 

Spleen,  176 

Malpighian  bodies  of,  177 

Spongioblasts,  262 

Spongioplasm,  29 

Sputa,  elastic  fibres  in,  438 
tubercle-bacilli  in,  433 

Staining,  methods  of,  418 
carmine,  alum-,  421 
borax-,  421 
lithio-,  421 
neutral,  420 
eosin,  420 

fuchsin,  carbol-,  423 
gentian-violet,  423 
Golgi's  methods,  427 
Gram's  solution,  424 
hsematoxylin,  418 
iron-haernatoxylin,  425 
methylene-blue,  422,  423 
Pal's  method,  426 
Van  Giesen's  stain,  425 

Stasis,  inflammatory,  298 

Starch,  tests  for,  436 

Stellate  cells,  245 
large,  245 
small,  245 

Stomach,  134 

Stomata,  46 
pseudo-,  47 

Stratum  granulosum,  198 
lucidium,  198 

Stratified  epithelium,  54 

Striated  muscles,  91 

Stropping,  method  of,  415 

Subrnaxillary  glands,  131 

Substance,  contractile,  83 

Suppuration,  296,  309 

Supra-renal  capsules,  186 

Sustentacular  cells  of  retina,  261 
of  testis,  227 

Sweat-glands,  198 

rFACTILE  corpuscles,  252 
1     Taste,  254 

-buds,  254 
Teasing,  400 

Technique,  microscopical,  399 
Teeth,  205 
Teledend rites,  234 
Teleneurites,  234 
Tendon,  80 
Testes,  225 
Tests  for  u  rates,  436 

amyloid  substance,  437 

calcium  oxalate,  436 

carbonates,  436 

cellulose,  436 

granules,  albuminoid,  436 
fatty,  436 


Tests  for  haemoglobin,  436 
iron,  437 

phosphates,  earthy,  436 
starch,  436 
Tissue,  adipose,  78 
areolar,  76 
cicatricial,  308 
connective,  63 
elementary,  41 

recognition  of,  43 
erectile,  222 
fibrous,  72 
fixation  of,  401 
fixed  elements  of,  303 
granulation-,  304 
lymphadenoid,  76 
mucous,  74 
muscular,  83 
necrosed,  fate  of,  295 
nervous,  94 

Tissues,  cardiac  muscular,  89 
preparation  of,  399 
by  cutting,  400 
by  maceration,  400 
regeneration  of,  334 
reticular,  76 
smooth  muscular,  83 
striated  muscular,  91 
Thrombo-phlebitis,  329 
Thrombosis,  329 
Thrombus,  329 
Thymus,  192 
Thyroid  gland,  181 
Thyro-iodine,  184 
Tongue,  129 
Tonsils,  143 
Touch,  252 
Trachea,  168 

Transitional  epithelium,  56 
Tubercle,  320 

-bacilli,  detection  of,  433 
Tubercular  ulcer,  322 
Tuberculosis,  319 
Tubes,  Fallopian,  210 

of  Henle,  155 
Tumors,  341 
angiomatous,  373 
hemangioma,  374 
lymphangioma,  371 
benign,  342 
classification  of,  345 
connective-tissue,  347 
chondroma,  350 
cylindroma,  356 
endothelioma,  355 
fibroma,  347 
keloid,  36_0 
lipoma,  350 
myxoma,  353 
osteoma,  353 
psammoma,  356 
sarcoma,  359 
giant-cell,  367 


448 


INDEX. 


Tumors,  connective-tissue,  sarcoma,  large 

round-cell,  364 
lympho-,  363 
melanotic,  369 
small  round-cell,  362 
spindle-cell,  365 
epithelial,  376 
adenoma,  376 
adeno-fibroma,  377 
cystic,  377 

intracanalicular,  378 
carcinoma,  382 

adeno-carcinoma,  390 
medullary,  384 
simple,  384 
scirrhous,  384 
colloid,  388 
cystoma,  392 
epithelioma,  391 
glioma,  394 
etiology  of,  342 
malignant,  343 
metastasis  of,  344 
mixed,  344 

morbid  changes  in,  344 
muscular,  370 
leiomyoma,  370 
rhabdomyoma,  372 
nomenclature  of,  345 
papillomata,  394 
Tunica  albuginea,  226 
vaginalis,  226 


Tunica,  granulosa,  209 
media,  112 

TTLCEK,  tubercular,  322 

U      Urates,  tests  for,  436 
Ureter,  164 
Urethra,  165 
Urinary  organs,  153 
Uterus,  211 

VACUOLES,  30 
contractile,  30 
Vagina,  216 
Van  Giesen's  stain,  425 
Vas  deferens,  225 
Vasa  efferentia,  233 

recta,  233 
Veins,  113 
Vesicles,  seminal,  225 


TITAKTS,  395 


White  corpuscles,  124 
fibres,  73 


VYLOL,  428 

A 

YELLOW  fibres,  73 
7ENKEE'S  fluid,  404 


Date  Due 


r 


P24 


I  QM551     Dunh 
D91              Hi 

1  1  ft  Qft  -            v,4 

on,   E.K. 
Jtology,  nor] 

D4658 
lal  and  mor- 

1  -LO  ?7O                      Ol 

i  • 

\L&*&£ 

•Pll  1941 

SEP  3- 

K  £xi/vr^ 

TP24  194\, 

Fp  18  1941 

V 

t»-F  —  Jt-AJ  —  lwn 

1 

, 

LIBRARY 

COLLEGE    OF    DENTISTRY 
UNIVERSITY    OF    CALIFORNIA 


